2-Aryl-2-halomethyl-4-alkenyl-1,3-dioxolanes

ABSTRACT

Novel compounds denoted as 2-aryl-2-halomethyl-4-alkenyl-1,3-dioxolanes used as intermediates in making 1-(2-Ar-4-R-1,3-dioxolan-2-ylmethyl)imidazoles, useful as antifungal and antibacterial agents.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation-in-part of our copending application Ser. No.710,994, filed Aug. 2, 1976, now abandoned; which in turn is a Divisionof Ser. No. 619,863, filed Oct. 6, 1975, now abandoned; which in turn isa continuation-in-part, Ser. No. 544,157, filed Jan. 27, 1975, issued asU.S. Pat. No. 3,936,470.

PRIOR ART

In U.S. Pat. Nos. 3,575,999 and 3,717,655 are described some1-(2-aryl-1,3-dioxolan-2-ylmethyl)imidazoles. The compounds of thepresent invention differ from the foregoing essentially by the nature ofthe R-substituent, present in the 4-position of the dioxolane group.

DESCRIPTION OF THE INVENTION

The invention relates to novel imidazole derivatives having the formula:##STR1## and the therapeutically acceptable acid addition salts thereof,wherein: Ar is a member selected from the group consisting of phenyl,substituted phenyl, thienyl, halothienyl and naphthyl, and wherein saidsubstituted phenyl is phenyl having from 1 to 3 substituentsindependently selected from the group consisting of halo, loweralkyl,loweralkyloxy, nitro and cyano; and

R is a member selected from the group consisting of alkyl having from 2to about 10 carbon atoms, alkyloxymethyl wherein the alkylgroup has from1 to about 10 carbon atoms, alkenyl, alkenyloxymethyl, wherein saidalkenyl has from 2 to about 10 carbon atoms, hydroxymethyl,2-propynyloxymethyl, halomethyl, aryl, arylloweralkyl, aryloxymethyl,arylthiomethyl and arylmethoxymethyl, wherein said aryl is a memberselected from the group consisting of phenyl, substituted phenyl,naphthyl, and mono- and di-halonaphthyl and wherein said substitutedphenyl is phenyl having from 1 to 3 substituents independently selectedfrom the group consisting of halo, loweralkyl, loweralkyloxy, cyano,nitro, phenyl, phenylmethyl, benzoyl, halobenzoyl, loweralkylcarbonyl,loweralkyloxycarbonyl and trifluoromethyl, provided that when more thanone substituents are present only one thereof may be selected from thegroup consisting of phenyl, phenylmethyl, benzoyl and halobenzoyl.

More particularly "alkyl" as used in the definition of R is meant toinclude straight and branch chained hydrocarbon radicals having from 2to about 10 carbon atoms, such as, for example, ethyl, propyl,1-methylethyl, 1,1-dimethylethyl, butyl, pentyl, hexyl, heptyl, octyl,decyl and the like alkyls; "alkyl" as used in the definition ofalkyloxymethyl is meant to include straight and branch chainedhydrocarbon radicals having from 1 to about 10 carbon atoms, such as,for example, methyl and the alkyls mentioned herebefore; "loweralkyl" asused herein has the meaning of a straight or branch chained alkylradical having from 1 to about 6 carbon atoms, such as, for example,methyl, ethyl, propyl, 1-methylethyl, 1,1-dimethylethyl, butyl, pentyl,hexyl and the like alkyls; "alkenyl" as used herein refers to straightand branch chained alkenyl radicals having from 2 to about 10 carbonatoms, such as, for example, ethenyl, 2-propenyl, 2-butenyl, 3-butenyl,2-pentenyl, 2-hexenyl, 2-decenyl and the like alkenyls; and the term"halo" is generic to halogens of atomic weight less than 127, i.e.,fluoro, chloro, bromo and iodo.

The compounds of formula (I) are conveniently prepared by reactingimidazole (II) with an appropriate reactive ester of formula (III)wherein Ar and R are as previously defined and wherein W is a reactiveester function, such as, for example, halo, 4-methylbenzenesulfonate,methylsulfonate and the like. Preferred reactive esters are halides andmore particularly bromides and chlorides.

In one method of conducting the reaction between imidazole and (III),imidazole is first transformed into a metal salt thereof by treatmentwith an appropriate metallating agent such as, for example, a metalalkoxide, e.g., sodium- or potassium methanolate, or a metal hydridesuch as sodium hydride. The thus obtained metal salt is then reactedwith (III) in an appropriate organic solvent, such as, for example,dimethylformamide or dimethylacetamide. A small amount of a metaliodide, such as sodium or potassium iodide may advantageously be addedto promote the reaction, especially when the reactive ester is achloride or bromide.

Alternatively, the reaction of imidazole with the reactive ester (III)may also be carried out without previous salt formation, by bringing thereactants into contact with each other in an appropriate organic solventsuch as, for example, dimethylformamide or dimethylacetamide. In thesecircumstances it is appropriate to use an excess of imidazole or to addto the reaction mixture an appropriate base such as, for example, sodiumor potassium carbonate or bicarbonate in order to bind the acid which isliberated during the course of the reaction. The use of an excess ofimidazole is however preferred. Further it is advantageous to conductthe reaction in the presence of a metal iodide such as, for example,sodium or potassium iodide.

In each of the above procedures, somewhat elevated temperatures may beemployed to enhance the rate of the reaction and most conveniently thereactions are carried out at the reflux temperature of the reactionmixture.

In these and the following preparations the reaction products may beisolated from the medium and, if necessary, further purified accordingto methodologies generally known in the art, such as, for example,extraction, trituration, crystallization, chromatography, etc..

The foregoing procedures are more fully illustrated by the followingschematic representation: ##STR2##

An additional method of preparing the compounds of formula (I) is by theketalization of an appropriate aroylmethylimidazole of formula (IV)wherein Ar has the same meaning as assigned to it previously with anappropriate diol of formula (V) wherein R is as previously defined.

Said ketalization reaction may be carried out following methodologiesanalogous to those described in the literature, e.g., for thepreparation of 2-bromomethyl-2,4-diphenyl-1,3-dioxolane [Synthesis,1974(I), 23].

In a preferred manner of carrying out the reaction both reactants arerefluxed together for several hours with azeotropic water removal in anappropriate organic solvent, preferably in the presence of a simplealcohol, such as, for example, ethanol, propanol, butanol, pentanol andthe like, and in the presence of an appropriate strong acid such as4-methylbenzenesulfonic acid. Suitable organic solvents are, forexample, aromatic hydrocarbons, such as benzene, methylbenzene,dimethylbenzene and the like and saturated hydrocarbons, such ascyclohexane. The foregoing reaction may be illustrated as follows:##STR3##

The compounds of formula (I) wherein R represents an alkyloxymethyl,alkenyloxymethyl, 2-propynyloxymethyl or arylmethoxymethyl radical,(I-a), may still by prepared by the reaction of an appropriate compoundof formula (I) wherein R is hydroxymethyl (I-b) with an appropriatereactive ester of formula (VI) wherein R¹ is selected from the groupconsisting of alkyl, alkenyl, 2-propynyl and arylmethyl and W is areactive ester function as previously defined, according to commonO-alkylating procedures. Preferably the reaction is carried out in asuitable organic solvent such as, for example, dimethylformamide ordimethylacetamide in the presence of an appropriate strong metal basesuch as, for example, sodium hydride, sodium carbonate, potassiumcarbonate and the like. ##STR4##

The compounds of formula (I) wherein R stands for alkyloxymethyl, (I-c),may still be prepared by the condensation of (I-b) with an appropriatealkanol. Said condensation reaction may be carried out by refluxing thereactants together under azeotropic water removal in an appropriateorganic solvent such as, for example, an aromatic hydrocarbon, e.g.,benzene, methylbenzene, dimethylbenzene and the like, a saturatedhydrocarbon, e.g., cyclohexane, or in the alkanol itself, in thepresence of an appropriate strong acid, such as, for example,4-methylbenzenesulfonic acid. ##STR5##

Those compounds of formula (I) wherein R represents alkyloxymethyl,alkenyloxymethyl, 2-propynyloxymethyl, arylmethoxymethyl oraryloxymethyl, (I-d), may still be prepared by the reaction of anappropriate reactive ester of formula (VII) wherein Ar and W are asdefined hereinbefore with an appropriate hydroxy compound of the formula(VIII) wherein R² is selected from the group consisting of alkyl,alkenyl, 2-propynyl, arylmethyl and aryl according to commonO-alkylating procedures as described herebefore. ##STR6##

The imidazole derivatives of formula (I), obtained in base form in theforegoing preparations, may be converted to their therapeutically usefulacid addition salts by reaction with an appropriate acid, as, forexample, an inorganic acid such as hydrohalic acid, i.e., hydrochloric,hydrobromic or hydroiodic acid; sulfuric, nitric or thiocyanic acid; aphosphoric acid; an organic base such as acetic, propanoic,hydroxyacetic, α-hydroxypropanoic, 2-oxopropanoic, ethanedioic,propanedioic, B 1,4-butanedioic, (Z)-2-butenedioic, (E)-2-butenedioic,2-hydroxy-1,4-butanedioic, 2,3-dihydroxy-1,4-butanedioic,2-hydroxy-1,2,3-propanetricarboxylic, benzoic, 3-phenylpropenoic,α-hydroxybenzeneacetic, methanesulfonic, ethanesulfonic,2-hydroxyethanesulfonic, 4-methylbenzenesulfonic 2-hydroxybenzoic,4-amino-2-hydroxybenzoic, 2-phenoxybenzoic or 2-acetyloxybenzoic acid.The salts are in turn converted to the corresponding free bases in theusual manner, e.g., by reaction with alkali such as sodium or potassiumhydroxide.

The intermediates of formula (III) may be prepared by subjecting anappropriate ketone of formula (IX), wherein Ar and W are as previouslydefined by a ketalization reaction with an appropriate diol of formula(V) in the same manner as described hereinbefore for the preparation ofthe compounds (I) starting from (IV) and (V). ##STR7##

Alternatively the intermediates of formula (III) are convenientlyprepared by transketalization of a ketal derivative of a ketone offormula (IX) such as, for example, a loweralkyl ketal or a cyclicloweralkylene ketal, with a glycol of formula (V) under conditionssimilar to those described hereinbefore for the direct ketalization. Theloweralkyl ketals and cyclic loweralkylene ketals used herein asstarting materials are easily obtained by ketalization of a ketone offormula (IX) with a lower alkanol or alkanediol according tomethodologies known in the art. A number of such compounds and methodsof preparing the same are described in U.S. Pat. Nos. 3,575,999 and3,717,655.

The intermediates of formula (III) wherein Ar and W are as previouslydefined an R is other than alkyl having 2-10 carbon atoms, provided thatwhen said Ar is phenyl, then said R is other than phenyl, are deemed tobe novel and as useful intermediates herein they constitute anadditional feature of this invention.

A number of the precursor glycols of formula (V) are known and they mayall be prepared according to known procedures as described in theliterature. In general, they may be derived from the corresponding2-R-oxiranes of formula (X) by hydrolytic cleavage of the oxiranenucleus with an appropriate strong acid such as, for example,ethanedioic acid, sulfuric acid, hydrochloric acid and the like.##STR8## The oxiranes of formula (X) may in turn be obtained in avariety of ways.

Those of formula (X-a), wherein R³ stands for alkyl or arylloweralkylmay, for example, be prepared by oxidizing an appropriate alkene orarylalkene of formula (XI) with an appropriate oxydizing agent such as,for example, a benzeneperoxoic acid, e.g., 3-chlorobenzeneperoxoic acid,##STR9## Alternatively intermediates of formula (X-a) may still beobtained by: i. converting an appropriate halide of formula (XII)wherein R⁴ is alkyl or arylloweralkyl, having one carbon less than inthe corresponding R³, into a Grignard complex with magnesium,

ii. reacting said Grignard complex with an appropriate2-halomethyloxirane of formula (XIII) to obtain a α-halomethyl alcoholcompound of formula (XIV); and

iii. performing ring closure of (XIV) by treatment with alkali, e.g.with sodium hydroxide in an appropriate solvent such as, for example,2,2'-oxybispropane.

The foregoing sequence of reactions is more fully illustrated in thefollowing schematic representation: ##STR10##

Those intermediates of formula (X) wherein R is alkyloxymethyl,alkenyloxymethyl, 2-propynyloxymethyl, arylmethoxymethyl oraryloxymethyl, (X-b), are conveniently obtained by the reaction of anappropriate hydroxycompound of formula (XV) wherein R⁵ is alkyl,alkenyl, 2-propynyl, aryl or arylmethyl with an appropriate2-halomethyloxirane of formula (XIII) following common O-alkylatingprocedures as generally known in the art.

Intermediates of formula (X) wherein R stands for arylthiomethyl, (X-c),may be prepared in an analogous manner by the S-alkylation of anarylthiol of formula (XVI) with a 2-halomethyloxirane of formula (XIII).

The foregoing reactions are schematically illustrated hereafter:##STR11##

Intermediates of formula (V) wherein R stands for alkenyl may, forexample, be prepared starting from an appropriatehydroxyalkylsubstituted ethanediol by ketalizing the ethanediol groupwith an appropriate ketone, e.g., 2-propanone, converting thereafter theremaining hydroxy group on the alkyl chain into a methanesulfonate groupby the reaction with methanesulfonyl chloride, splitting offmethanesulfonic acid by treatment with an appropriate strong base suchas, for example, sodium hydride in a suitable solvent such asdimethylformamide, and finally liberating the free diol from the ketalby treatment with an appropriate strong mineral acid such as, forexample, hydrochloric or sulfuric acid.

In a preferred manner of carrying out the aforementioned reactions, theketone used in the ketalization step is an intermediate of formula (IX)whereby the alkenylsubstituted dioxolanes of formula (III) are directlyobtained in the course of the foregoing reaction sequence.

The precursor arylketones of formula (IX) are generally known and may beprepared according to known procedures as described in the literature.Bromides are, for example, easily obtained by the bromination of thecorresponding methyl aryl methanone with bromine.

The aroylmethylsubstituted imidazoles of formula (IV), a number of whichare described in U.S. Pat. Nos. 3,717,655 and 3,658,813, areconveniently prepared by the reaction of (IX) with imidazole in ananalogous manner as previously described for the preparation of thecompounds (I) starting from imidazole and (III).

The reactive esters of formula (VII), used as intermediates in thepreparation of the compounds (I-d) are easily obtained by converting thecorresponding alcohol of formula (I-b) into a reactive ester thereofaccording to methodologies generally known in the art. For example,methanesulfonates and 4-methylbenzenesulfonates are convenientlyprepared by the reaction of the alcohol with respectivelymethanesulfonyl chloride or 4-methylbenzenesulfonyl chloride and halidesmay be prepared by the reaction of the alcohol with an appropriatehalogenating agent such as, for example, sulfuryl chloride, phosphorpentachloride, phosphor pentabromide, phosphoryl chloride and the like.When the reactive ester is an iodide, it is preferably prepared from thecorresponding chloride or bromide by the replacement of that halogenwith iodine.

From formula (I) it is evident that the compounds of this invention havetwo asymmetric carbon atoms in their structures, namely those located inthe 2- and 4-position of the dioxolane nucleus, and consequently theyexist under different stereochemical optical isomeric forms. Thestereochemical optical isomeric forms of (I) and the therapeuticallyactive acid addition salts thereof are intended to be within the scopeof this invention.

The diastereomeric racemates of (I), denotes as cis and trans formsrespectively, according to the rules described in "Naming and Indexingof Chemical Substances for Chemical Abstracts during the 9th CollectivePeriod (1972-1976)", published in C. A. 1972, 76, Index Guide SectionIV, p. 85, may be obtained separately by conventional methods.Appropriate methods which may advantageously be employed thereforeinclude, for example, selective crystallization andcolumn-chromatography. For a number of compounds the stereochemicalconfiguration was experimentally determined. In the remaining cases itis conventionally agreed to designate the stereochemical form which isfirst isolated as "A" and the second as "B", without further referenceto the actual stereochemical configuration.

Since the asymmetric carbon atoms are already present in theintermediates (III) it is also possible to separate cis and trans forms,or generally "A" and "B" forms at this stage, whereupon thecorresponding forms of (I) may be obtained after reaction of theforegoing with imidazole as previously described. The separation of cisand trans forms of (III) may be performed by conventional methods asdescribed hereinbefore for the separation of the compounds (I) intotheir cis and trans forms. When R in the intermediate of formula (III)has the meaning of a hydroxymethyl group it may be advantageous toesterify first said hydroxymethyl group with an appropriate acylhalide,e.g., benzoyl chloride whereupon the thus obtained esters are separatedinto their cis and trans forms, from which the acyl group issubsequently split off hydrolytically in alkaline medium yielding thecorresponding forms of the desired hydroxymethylsubstitutedintermediates of formula (III).

It is evident that the cis and trans diastereomeric racemates may befurther resolved into their optical isomers, cis (+), cis (-), trans (+)and trans (-) by the application of methodologies known to those skilledin the art.

The compounds of formula (I) and the acid addition salts thereof areuseful agents in combatting fungi and bacteria. As such they arevaluable in the treatment of human beings, animals and plants sufferingfrom pathogenic microorganisms and in the destruction of microorganismson materials. The broad spectrum of antifungal and antibacterialactivity of the compounds of formula (I) is clearly illustrated by theexperimental data presented hereafter. The compounds in the tables arenot listed for the purpose of limiting the invention thereto, but onlyin order to exemplify the useful properties of all the compounds withinthe scope of formula (I).

The test for antifungal activity was performed using Sabouraud's liquidmedium in test tubes each containing 4.5 ml of liquid medium, autoclavedat 120° C. for 15 minutes. The substances were dissolved in 50% ethanolat a concentration of 20mg/ml and subsequently diluted with steriledistilled water to a concentration of 10mg/ml. Successive decimaldilutions were then made with distilled water to give a series of stocksolutions. To each tube containing 4.5 ml of Sabouraud's liquid mediumwas added 0.5 ml of one of the stock solutions to give a concentrationof the drug under investigation of 100 μg, 10 μg, 1 μg or 0.1 μg per mlof medium. Filamentous fungi were incubated at 25° C. for 2-3 weeks. Asquare block of side 2 mm. was excised and inoculated into the liquidmedium. A three-day old culture on Sabouraud's liquid medium was usedfor yeasts, and the inoculum was 0.05 ml per tube. All the cultures wereincubated at 25° C. for 14 days. The final readings were taken after twoweeks and are summarized in the Tables A as follows:

++++ = complete inhibition of growth at 0.1 μg/ml

+++ = complete inhibition of growth at 1 μg/ml

+++ = complete inhibition of growth at 10 μg/ml

+ = complete inhibition of growth at 100 μg/ml

0 = no effect, i.e. growth was observed at the highest concentrationtested (100 μg/ml). In a first screening the drugs under investigationwere tested against the following 11 fungi:

1. Microsporum canis (M. c. in the tables)

2. Ctenomyces mentagrophytes (Ct. m. in the tables)

3. Trichophyton rubrum (Tr. r. in the tables)

4. Phialophora verrucosa (Ph. v. in the tables)

5. Cryptococcus neoformans (Cr. n. in the tables)

6. Candida tropicalis (C. tr. in the tables)

7. Candida albicans (C. alb. in the tables)

8. Mucor species (Muc. in the tables)

9. Aspergillus fumigatus (A. f. in the tables)

10. Sporotrichum schenckii (Sp. s. in the tables)

11. Saprolegnia species (Sap. in the tables)

A number of the substances showing activity against the PhycomycetesMucor at the 10 μg/ml concentration were also tested against four otherspecies of phycomycetes, namely:

1. Absidia ramosa (Abs. r. in the tables)

2. Basidiobolus meristosporus (Bas. m. in the tables)

3. Mortierella species (Mort. in the tables)

4. Rhizopus (Rhi. in the tables).

The method used in this second screen was exactly the same as describedabove, and the results are given in Tables B.

Bactericidal tests were performed on cultures on phenol red dextrosebroth Difco medium. The same decimal dilution techniques as describedherebefore were used. The inoculum consisted of a platinum loop (5 mm.diameter) from a 24 hour broth culture. 48 Hours after incubation,subcultures were made from each culture and for the assessment of thebactericidal activity of the drugs under investigation the presence orabsence of growth after 7 days incubation was scored as described above.

The substances were tested against the following gram-negative bacilli:

1. Salmonella pullorum gallinarum (SPG in the table)

2. Escherichia coli (E. coli in the table), and

3. Pseudomonas aeruginosa (Ps. aer. in the table);

and against the following gram-positive bacilli and cocci:

1. Erysipelothrix insidiosa (E. ins. in the table),

2. Staphylococcus hemolyticus (Staph. in the table), and

3. Streptococcus pyogenes (Strept. in the table).

The results are summarized in Tables C.

                                      Tables A1                                   __________________________________________________________________________    ANTIFUNGAL ACTIVITY.                                                           ##STR12##                                                                              ANTIFUNGAL ACTIVITY                                                           M. c.                                                                              Ct. m.                                                                             Tr. r.                                                                             Ph. v.                                                                            Cr. n.                                                                            C. tr.                                                                            C. alb.                                                                           Muc.                                                                              A.f.                                                                              Sp. s.                                                                            Sap.                     R.sub.1                                                                            R.sub.2                                                                            (1)  (2)  (3)  (4) (5) (6) (7) (8) (9) (10)                                                                              (11)                     __________________________________________________________________________    4-Cl 4-Cl ++++ ++++ ++++ +   +++ ++  +   +++ +++ ++  ++                       4-Cl H    ++   +++  +++  +   ++  0   +   +   ++  ++  +                        4-Cl 2,4-(Cl).sub. 2                                                                    ++   +++  +++  +   ++  0   +   +   +   ++  +                        4-Br 4-Cl +++  +++  +++  +   +   +   0   0   ++  ++  +                        4-Br 2,4-(Cl).sub.2                                                                     ++   ++   +++  0   0   0   0   +   0   +   0                        2,4-(Cl).sub.2                                                                     H    +++  +++  +++  +   +   0   +   +   +++ ++  +                        4-OCH.sub.3                                                                        4-Cl +++  +++  ++   +   0   0   0   +   +++ ++  +                        H    2,4-(Cl).sub.2                                                                     ++   +++  +++  +   ++  0   0   +   ++  ++  +                        2,4-(Cl).sub.2                                                                     4-Cl +++  +++  +++  +   +++ ++  +   +++ +++ ++  +                        H    4-Cl +++  +++  +++  +   ++  +   0   +   ++  ++  +                        4-Cl 2-Cl ++   +++  +++  +   ++  0   0   +   +   +++ ++                       2-Cl 2,4-(Cl).sub.2                                                                     +++  +++  +++  +   +++ 0   0   0   +++ +++ ++                       4-Br 2-Cl +++  +++  +++  +   +++ 0   +   ++  +   ++  +                        2-Cl 4-Cl +++  +++  +++  +   +   +   +   +   +++ ++  ++                       2,4-(Cl).sub.2                                                                     2,4-(Cl).sub.2                                                                     ++   +++  +++  +   +++ 0   0   +   +++ ++  +                        4-Br H    +++  +++  +++  +   ++  0   +   +   +   +   +                        H    4-Br +++  +++  +++  +   ++  0   +   +   ++  ++  +                        4-CH.sub.3                                                                         2,4-(Cl).sub.2                                                                     ++   +++  +++  +   ++  0   0   +   +   ++  +                        4-Br 4-Br +++  +++  +++  +   +++ +   0   ++  +++ ++  +                        2,4-(Cl).sub.2                                                                     2-Cl ++   +++  +++  +   +++ +   +   +   +   ++  +                        4-CH.sub.3                                                                         4-Cl +++  +++  +++  +   +++ +   0   + + +++ ++  +                        2,4-(Cl).sub.2                                                                     4-Br +++  +++  +++  +   +++ ++  +   +++ +++ ++  +                        4-Cl 4-Br +++  +++  +++  +   +++ ++   ++ ++  +++ ++  +++                      4-CH.sub.3                                                                         4-Br +++  +++  +++  0   0   0   0   0   +++ 0   ++                       3-Cl 2,4-(Cl).sub.2                                                                     +    ++   +++  0   +   0   0   +   +   ++  +                        2-Cl 4-Br +++  +++  +++   ++ +++ ++  +   ++  +++ ++  ++                       4-CH.sub.3                                                                         2-Cl ++   +++  +++  +   +   0   0   +   +   ++  +                        4-Cl 4-CH.sub.3                                                                         +++  +++  +++  +   +++ 0   +   +   +++ ++  +                        4-Br 4-CH.sub.3                                                                         +++  ++   +++  +   ++  0    ++ ++  +++ ++  +                        4-Cl 4-F  +++  +++  +++  +   ++  +   +   ++  +++ ++  +                        4-Br 4-F  +++  +++  +++  +   ++  +   +   +++ +++ ++  +                        __________________________________________________________________________

                                      tables A2                                   __________________________________________________________________________    ANTIFUNGAL ACTIVITY.                                                           ##STR13##                                                                                     ANTIFUNGAL ACTIVITY                                                           M. c.                                                                              Ct. m.                                                                             Tr. r.                                                                             Ph. v.                                                                            Cr. n.                                    R.sub.1                                                                            R.sub.2 Isomer                                                                            (1)  (2)  (3)  (4) (5)                                       __________________________________________________________________________    4-Cl 2-CH.sub.3, 4-Cl                                                                      cis 0    ++   ++   0   +                                         4-Cl 4-CH.sub.3                                                                            trans                                                                             ++   ++++ +++  ++  +++                                       4-Cl 2-CH.sub.3,4-Cl                                                                       trans                                                                             +    +++  +++  0   ++                                        4-Cl 4-CH.sub.3                                                                            cis +++  ++++ ++++ ++  +++                                       4-Cl 4-Cl    A   +++  ++++ ++++ 0   ++                                        4-Cl 4-Cl    B   ++   ++++ +++  +   +                                         4-Cl 4-F     cis +++  ++++ ++++ +   +                                         4-Cl 2-CH.sub.3                                                                            A   ++   +++  +++  +   ++                                        4-Cl 2-Cl    A   0    +++  +++  0   ++++                                      4-Cl 2-CH.sub.3                                                                            B   ++   ++++ ++++ +   ++                                        4-Cl 2,4-(Cl).sub.2                                                                        B   ++   +++  +++  0   ++                                        4-Cl 4-OCH.sub.3                                                                           A   +++  ++++ ++++ +   +++                                       4-Cl 4-F     trans                                                                             ++   ++++ +++  +   ++                                        4-Cl 4-OCH.sub.3                                                                           B   +    +++ +                                                                              ++   +   ++                                        4-Cl 2,6-(Cl).sub.2                                                                        A   +    ++++ ++++ 0   ++                                        4-Cl 2-Cl    B   ++   +++  ++++ +   ++                                        4-Cl 2,6-(Cl).sub.2                                                                        B   ++   ++   +++  +   +                                         2,4-(Cl).sub.2                                                                     4-CH.sub.3                                                                            B   ++   ++   ++   +   ++                                        2,4-(Cl).sub.2                                                                     4-F     A   ++   ++   ++   ++  ++                                        2,4-(Cl).sub.2                                                                     2-CH.sub.3                                                                            A   +++  +++  +++  +   +++                                       2,4-(Cl).sub.2                                                                     4-CH.sub.3                                                                            A   ++   +++  +++  ++  +++                                       2,4-(Cl).sub.2                                                                     4-OCH.sub.3                                                                           A   ++++ ++++ ++++ ++  ++++                                      2,4-(Cl).sub.2                                                                     4-Cl    cis ++++ ++++ ++++ ++  ++++                                      2,4-(Cl).sub.2                                                                     2-CH.sub.3                                                                            B   ++   +++  +++  +   ++                                        2,4-(Cl).sub.2                                                                     2,4-(Cl).sub.2                                                                        A   ++   +++  +++  0   +++                                       2,4-(Cl).sub.2                                                                     4-Cl    trans                                                                             ++   +++  +++  +   ++                                        2,4-(Cl).sub.2                                                                     4-Br    A   ++   +++  +++  +   +++                                       2,4-(Cl).sub.2                                                                     2,4-(Cl).sub.2                                                                        B   ++   +++  +++  +   ++                                        2,4-(Cl).sub.2                                                                     H       A   +++  +++  +++  ++  +++                                       2,4-(Cl).sub.2                                                                     3,4-(Cl).sub.2                                                                        A   +++  +++  +++  +   +++                                       2,4-(Cl).sub.2                                                                     3-Cl    A   +++  +++  +++  +   +++                                       2,4-(Cl).sub.2                                                                     2-Cl    A   +++  +++  +++  +   +++                                       2,4-(Cl).sub. 2                                                                    2-CH.sub.3, 4-Cl                                                                      A + B                                                                             +++  +++  +++  0   +++                                       2,4-(Cl).sub.2                                                                     2-Cl    B   ++   +++  +++  0   ++                                        2,4-(Cl).sub.2                                                                     2,6-(Cl).sub.2                                                                        A   ++   +++  +++  +   +++                                       2,4-(Cl).sub.2                                                                     3,5-(CH.sub.3).sub.2, 4-Cl                                                            A   0    0    ++   0   0                                         2,4-(Cl).sub.2                                                                     2,4-(Br).sub.2                                                                        A   0    0    +    0   +++                                       2,4-(Cl).sub.2                                                                     4-CN    A   +++  +++  +++  ++  +++                                       2,4-(Cl).sub.2                                                                     2-Br    cis ++   +++  +++  0   +++                                       2,4-(Cl).sub.2                                                                     2-OCH.sub.3                                                                           A   ++   +++  +++  +   +++                                       2,4-(Cl).sub.2                                                                     2-Br    trans                                                                             ++   +++  ++   0   +++                                       2,4-(Cl).sub.2                                                                     2,4,6-(Cl).sub.3                                                                      A   0    +++  ++   0   + ++                                      2,4-(Cl).sub.2                                                                     2,5-(CH.sub.3).sub.2                                                                  A   +++  +++  +++  0   +++                                       2,4-(Cl).sub.2                                                                     2,5-(CH.sub.3).sub.2                                                                  B   ++   ++   +++  0   ++                                        2,4-(Cl).sub.2                                                                     2-Cl,4-tert. but.                                                                     A   0    +    ++++ 0   ++++                                      2,4-(Cl).sub.2                                                                     2,4,5-(Cl).sub.3                                                                      A   0    0    0    0   0                                         2,4-(Cl).sub.2                                                                     2-Cl,4-tert. but.                                                                     B   +    +    +    0   +                                         2,4-(Cl).sub.2                                                                     2,4,5-(Cl).sub.3                                                                      B   +    ++   ++   0   +                                         2,4-(Cl).sub.2                                                                     2,5-(Br).sub.2,4-CH.sub.3                                                             A   +    ++   ++++ 0   ++++                                      2,4-(Cl).sub.2                                                                     2-F     A   ++   ++++ ++++ +   ++++                                      4-CH.sub.3                                                                         4-Br    A   ++++ ++++ ++++ ++  ++++                                      4-Cl 4-Br    A   ++++ ++++ ++++ + + ++++                                      4-Br 4-Br    A   ++++ ++++ ++++ +   ++++                                      2,4-(Cl).sub.2                                                                     2-OC.sub.2 H.sub.5                                                                    A   ++   ++++ ++++ +   ++++                                      2-Cl 4-Br    A + B                                                                             ++   ++++ ++   ++  ++++                                      2-Cl 4-Br    B   ++   ++++ ++++ ++  ++++                                      H    4-Br    A   ++   ++++ ++++ +   ++++                                      2-Br 4-Br    A   ++   ++++ ++++ ++  ++++                                      2-Br 4-Br    B   ++   ++++ ++++ ++  ++                                        2,4-(Cl).sub.2                                                                     4-C.sub.6 H.sub.5                                                                     A + B                                                                             0    ++++ ++++ 0   + +++                                     2,4-(Cl).sub.2                                                                     4-C.sub.6 H.sub.5                                                                     B   0    0    0    0   0                                         2,4-(Cl).sub.2                                                                     2,6-(CH.sub.3).sub.2                                                                  A   ++++ ++++ ++++ 0   +                                         2,4-(Cl).sub.2                                                                     4-Br    B   ++   ++++ ++++ +   0                                         2,4-(Cl).sub.2                                                                     2,6-(CH.sub.3).sub.2                                                                  A + B                                                                             ++   ++++ ++++ 0   0                                         2,4-(Cl).sub.2                                                                     3,5-(CH.sub.3).sub.2                                                                  A   +++  +++  +++  0   +++                                       2,4-(Cl).sub.2                                                                     4-iC.sub.3 H.sub.7                                                                    A + B                                                                             +++  +++  +++  +   +++                                       2,4-(Cl).sub.2                                                                     2-Cl,6-CH.sub.3                                                                       A   +++  +++  +++  +   +++                                       2,4-(Cl).sub.2                                                                     4-tert.but.                                                                           A   ++   ++++ ++++ 0   ++                                        2,4-(Cl).sub.2                                                                     3,5-(Cl).sub.2                                                                        A   ++++ ++++ +++ +                                                                              0   0                                         2,4-(Cl).sub.2                                                                     3-CH.sub.3,4-Cl                                                                       A   ++++ ++++ ++++ +   ++++                                                       ANTIFUNGAL ACTIVITY                                                           C.tr.                                                                             C. alb.                                                                           Muc.                                                                              A.f. Sp. s.                                                                             Sap.                                   R.sub.1                                                                            R.sub.2 Isomer                                                                            (6) (7) (8) (9)  (10) (11)                                   __________________________________________________________________________    4-Cl 2-CH.sub.3, 4-Cl                                                                      cis 0   0   0   0    0    0                                      4-Cl 4-CH.sub.3                                                                            trans                                                                             0   +   +   ++   ++   ++                                     4-Cl 2-CH.sub.3,4-Cl                                                                       trans                                                                             0   0   ++  +    ++   +                                      4-Cl 4-CH.sub.3                                                                            cis 0   0   +   +++  +++  ++                                     4-Cl 4-Cl    A   0   0   +   +++  0    +                                      4-Cl 4-Cl    B   0   0   ++  ++   ++   ++                                     4-Cl 4-F     cis 0   0   ++  ++   ++   ++                                     4-Cl 2-CH.sub.3                                                                            A   0   +   ++  ++   ++                                          4-Cl 2-Cl    A   0   0   0   0    0    0                                      4-Cl 2-CH.sub.3                                                                            B   0   +   0   ++   ++   +                                      4-Cl 2,4-(Cl).sub.2                                                                        B   0   0   ++  ++   ++   +                                      4-Cl 4-OCH.sub.3                                                                           A   0   0   0   ++   ++   ++                                     4-Cl 4-F     trans                                                                             0   0   +   +    +    ++                                     4-Cl 4-OCH.sub.3                                                                           B   0   0   0   +    ++   ++                                     4-Cl 2,6-(Cl).sub.2                                                                        A   0   0   ++  ++   ++   +                                      4-Cl 2-Cl    B   0   0   0   ++   ++   +                                      4-Cl 2,6-(Cl).sub.2                                                                        B   0   0   +   ++   +    0                                      2,4-(Cl).sub.2                                                                     4-CH.sub.3                                                                            B   0   0   +   ++   ++   ++                                     2,4-(Cl).sub.2                                                                     4-F     A   ++  0   +   ++   ++   ++                                     2,4-(Cl).sub.2                                                                     2-CH.sub.3                                                                            A   0   0   +++ ++   ++   +                                      2,4-(Cl).sub.2                                                                     4-CH.sub.3                                                                            A   0   0   +++ +++  +++  ++                                     2,4-(Cl).sub.2                                                                     4-OCH.sub.3                                                                           A   0   0   ++  ++   ++++ +++                                    2,4-(Cl).sub.2                                                                     4-Cl    cis 0   0   +++ ++   +++  ++                                     2,4-(Cl).sub.2                                                                     2-CH.sub.3                                                                            B   0   0   ++  ++   ++   +                                      2,4-(Cl).sub.2                                                                     2,4-(Cl).sub.2                                                                        A   0   0   0   0    ++   +                                      2,4-(Cl).sub.2                                                                     4-Cl    trans                                                                             0   0   ++  ++   ++   +                                      2,4-(Cl).sub.2                                                                     4-Br    A   +++ 0   ++  +++  ++   ++                                     2,4-(Cl).sub.2                                                                     2,4-(Cl).sub.2                                                                        B   0   0   +   +    ++   +                                      2,4-(Cl).sub.2                                                                     H       A   ++  0   ++  +++  +++  ++                                     2,4-(Cl).sub.2                                                                     3,4-(Cl).sub.2                                                                        A   0   0   ++  +++  +++  +                                      2,4-(Cl).sub.2                                                                     3-Cl    A   ++  0   ++  +++  +++  +                                      2,4-(Cl).sub.2                                                                     2-Cl    A   ++  +   ++  +++  +++  +                                      2,4-(Cl).sub.2                                                                     2-CH.sub.3,4-Cl                                                                       A + B                                                                             0   0   ++  ++   ++   +                                      2,4-(Cl).sub.2                                                                     2-Cl    B   0   0   0   +    ++   +                                      2,4-(Cl).sub.2                                                                     2,6-(Cl).sub.2                                                                        A   0   0   0   ++   ++   +                                      2,4-(Cl).sub.2                                                                     3,5-(CH.sub.3).sub.2,4-Cl                                                             A   0   0   0   0    0    0                                      2,4-(Cl).sub.2                                                                     2,4-(Br).sub.2                                                                        A   0   0   0   0    0    0                                      2,4-(Cl).sub.2                                                                     4-CN    A   ++  0   0   ++   +    ++                                     2,4-(Cl).sub.2                                                                     2-Br    cis 0   0   +++ ++   ++   +                                      2,4-(Cl).sub.2                                                                     2-OCH.sub.3                                                                           A   +   0   0   ++   ++   +                                      2,4-(Cl).sub.2                                                                     2-Br    trans                                                                             0   0   +   ++   ++   +                                      2,4-(Cl).sub.2                                                                     2,4,6-(Cl).sub.3                                                                      A   +   0   0   0    0    0                                      2,4-(Cl).sub.2                                                                     2,5-(CH.sub.3).sub.2                                                                  A   0   0   +   ++   ++   +                                      2,4-(Cl).sub.2                                                                     2,5-(CH.sub.3).sub.2                                                                  B   0   0   0   ++   +    +                                      2,4-(Cl).sub.2                                                                     2-Cl,4-tert.but.                                                                      A   0   0   0   0    0    0                                      2,4-(Cl).sub.2                                                                     2,4,5-(Cl).sub.3                                                                      A   0   0   0   0    0    0                                      2,4-(Cl).sub.2                                                                     2-Cl,4-tert.but.                                                                      B   0   0   0   +    0    0                                      2,4-(Cl).sub.2                                                                     2,4,5-(Cl).sub.3                                                                      B   0   0   0   0    0    0                                      2,4-(Cl).sub.2                                                                     2,5-(Br).sub.2,4-CH.sub.3                                                             A   0   0   +   +    +    0                                      2,4-(Cl).sub.2                                                                     2-F     A   ++  +   ++  ++++ ++++ ++                                     4-CH.sub.3                                                                         4-Br    A   +   0   0   ++++ ++++ ++                                     4-Cl 4-Br    A   0   0   0   ++++ ++   +                                      4-Br 4-Br    A   0   0   0   +    +    ++                                     2,4-(Cl).sub.2                                                                     2-OC.sub.2 H.sub.5                                                                    A   +   0   0   ++   ++   +                                      2-Cl 4-Br    A + B                                                                             +   +   0   ++   ++   ++                                     2-Cl 4-Br    B   0   +   +   +    ++++ ++                                     H    4-Br    A   0   0   0   ++   ++   ++                                     2-Br 4-Br    A   ++  +   ++  ++   ++   ++                                     2-Br 4-Br    B   0   0   0   ++   +'++ ++                                     2,4-(Cl).sub.2                                                                     4-C.sub.6 H.sub.5                                                                     A + B                                                                             0   0   0   0    0    0                                      2,4-(Cl).sub.2                                                                     4-C.sub.6 H.sub.5                                                                     B   0   0   0   0    0    0                                      2,4-(Cl).sub.2                                                                     2,6-(CH.sub.3).sub.2                                                                  A   +   0   +   ++   +    +                                      2,4-(Cl).sub.2                                                                     4-Br    B   0   0   ++  +    ++++ +                                      2,4-(Cl).sub.2                                                                     2,6-(CH.sub.3).sub.2                                                                  A + B                                                                             0   0   +   +    ++   0                                      2,4-(Cl).sub.2                                                                     3,5-(CH.sub.3).sub.2                                                                  A   0   0   0   ++   0    0                                      2,4-(Cl).sub.2                                                                     4-iC.sub.3 H.sub.7                                                                    A + B                                                                             +++ 0   +   +++  +++  +                                      2,4-(Cl).sub.2                                                                     2-Cl,6-CH.sub.3                                                                       A   +++ +   + ++                                                                              +++  +++  +                                      2,4-(Cl).sub.2                                                                     4-tert.but.                                                                           A   0   0   0   +    +    0                                      2,4-(Cl).sub.2                                                                     3,5-(Cl).sub.2                                                                        A   0   0   ++  ++   0    0                                      2,4-(Cl).sub.2                                                                     3-CH.sub.3,4-Cl                                                                       A   0   0   +   ++++ ++   +                                      __________________________________________________________________________

                                      tables A3                                   __________________________________________________________________________    ANTIFUNGAL ACTIVITY                                                            ##STR14##                                                                                 ANTIFUNGAL ACTIVITY                                                           M. c.                                                                              Ct. m.                                                                             Tr. R.                                                                             Ph. V.                                                                            Cr. n.                                                                             C. tr.                                                                            C. alb.                                                                           Muc.                                                                              A.f.                                                                              Sp.                                                                                Sap.                R.sub.1                                                                            R.sub.2                                                                           Isomer                                                                            (1)  (2)  (3)  (4) (5)  (6) (7) (8) (9) (10) (11)                __________________________________________________________________________    2,4-(Cl).sub.2                                                                     4-Br                                                                              A + B                                                                             ++++ ++++ ++++ +   ++++ ++  +   ++  ++  ++++ +                   2,4-(Cl).sub.2                                                                     H   A + B                                                                             ++++ ++++ ++++ + + ++++ ++  +   +++ ++  ++++ ++                  __________________________________________________________________________

                                      tables A4                                   __________________________________________________________________________     ##STR15##                                                                                  ANTIFUNGAL ACTIVITY                                                           M. c.                                                                              Ct. m.                                                                             Tr. R.                                                                             Ph. V.                                                                            Cr. n.                                                                             C. tr.                                                                            C. alb.                                                                           Muc.                                                                              A.f. Sp.                                                                                Sap.              R.sub.1                                                                            R.sub.2                                                                            Isomer                                                                            (1)  (2)  (3)  (4) (5)  (6) (7) (8) (9)  (10) (11)              __________________________________________________________________________    2,4-(Cl).sub.2                                                                     2-Cl     ++++ ++++ ++++ +   ++++ ++  0   ++  ++++ ++   +                 2,4-(Cl).sub.2                                                                     2,4-(Cl).sub.2                                                                         ++   ++++ ++++ 0   ++++ ++  0   ++  ++   ++   +                 2,4-(Cl).sub.2                                                                     2,6-(Cl).sub.2                                                                     A + B                                                                             ++   ++++ ++++ 0   ++++ 0   0   ++  ++   ++   0                 2,4-(Cl).sub.2                                                                     4-OCH.sub.3                                                                        A + B                                                                             ++++ ++++ ++++ +   ++++ ++  0   0   ++++ ++   +                 2,4-(Cl).sub.2                                                                     4-Cl     ++++ ++++ ++++ +   ++++ ++  ++  ++  ++   ++++ +                 2,4-(Cl).sub.2                                                                     H        ++++ ++++ ++++ +   ++++ ++  +   ++  ++++ ++++                   __________________________________________________________________________                                                                +                                                                             2             

                                      tables A5                                   __________________________________________________________________________    ANTIFUNGAL ACTIVITY                                                            ##STR16##                                                                                       ANTIFUNGAL ACTIVITY                                                           M. c.                                                                             Ct. m.                                                                            Tr. r.                                                                            Ph. v.                                                                            Cr. n.                                                                            C. tr.                                                                            C. alb.                                                                           Muc.                                                                              A.f.                                                                              Sp.                                                                               Sap.               Ar           R     (1) (2) (3) (4) (5) (6) (7) (8) (9) (10)                                                                              (11)               __________________________________________________________________________    2,4-Cl.sub.2C.sub.6 H.sub.3                                                                C.sub.2 H.sub.5                                                                     +++ +++ +++ ++  +++ +++ o   +   +++ ++  ++                 2-ClC.sub.6 H.sub.4                                                                        C.sub.2 H.sub.5                                                                     +++ +++ +++ +   +   +   o   o   ++  +   ++                 2-CH.sub.3C.sub.6 H.sub.4                                                                  C.sub.2 H.sub.5                                                                     ++  +++ +++ +   +   +   o   o   ++  +   +                  4-CH.sub.3C.sub.6 H.sub.4                                                                  C.sub.2 H.sub.5                                                                     ++  +++ +++ +   +   +   o   o   +   o   +                  2,3,4-(Cl).sub.3C.sub.6 H.sub.2                                                            C.sub.2 H.sub.5                                                                     +++ +++ +++ +   +   +   ++  +   ++  ++  +                  2-BrC.sub.6 H.sub.4                                                                        C.sub.2 H.sub.5                                                                     +++ +++ +++ +   +   +   +   o   +++ ++  ++                 2,3-(Cl).sub.2C.sub.6 H.sub.3                                                              C.sub.2 H.sub.5                                                                     +++ +++ +++ +   +   o   +   o   ++  +   +                  2-Cl,4-FC.sub.6 H.sub.3                                                                    C.sub.2 H.sub.5                                                                     +++ +++ +++ +   ++  ++  +   o   +++ ++  ++                 4-BrC.sub.6 H.sub.4                                                                        C.sub.2 H.sub.5                                                                     +++ +++ +++ +   +   +   +   o   ++  +   +                  3-ClC.sub.6 H.sub.4                                                                        C.sub.2 H.sub.5                                                                     ++  +++ +++ +   +   o   +   o   +   +   +                  2-Cl,4-BrC.sub.6 H.sub.3                                                                   C.sub.2 H.sub.5                                                                     +++ +++ +++ +   ++  ++  +   +   +++ ++  ++                 2,4-(Br).sub.2C.sub.6 H.sub.3                                                              C.sub.2 H.sub.5                                                                     +++ +++ +++ ++  +++ ++  o   +   +++ ++  ++                 4-OCH.sub.3C.sub.6 H.sub.4                                                                 C.sub.2 H.sub.5                                                                     ++  ++  +++ o   o   o   o   o   +   o   +                  2-thienyl    C.sub.2 H.sub.5                                                                     +++ +++ +++ +   o   +   o   o   +   o   +                  2-CH.sub.3,4-ClC.sub.6 H.sub.3                                                             C.sub.2 H.sub.5                                                                     +++ +++ +++ ++  +++ ++  +   o   +++ ++  +++                2-Cl,4-OCH.sub.3C.sub.6 H.sub.3                                                            C.sub.2 H.sub.5                                                                     +++ +++ +++ +   +   +   o   o   +++ +   +                  3,4,5-(Cl).sub.3C.sub.6 H.sub.2                                                            C.sub.2 H.sub.5                                                                     ++  ++  +++ +   +   o   +   +   +   +   +                  2-naphthyl   C.sub.2 H.sub.5                                                                     ++  +++ +++ +   +   o   o   +   +   +   +                  5-Cl-2-thienyl                                                                             C.sub.2 H.sub.5                                                                     ++  +++ +++ +   +   +   o   o   ++  +   +                  2,4-(Cl).sub.2C.sub.6 H.sub.3                                                              nC.sub.3 H.sub.7                                                                    +++ +++ +++ ++  +++ ++  +   ++  +++ ++  ++                 2,4-(Cl).sub.2C.sub.6 H.sub.3                                                              nC.sub.4 H.sub.9                                                                    +++ ++  +++ ++  +++ ++  o   +   +++ +++ ++                 2,4-(Cl).sub.2C.sub.6 H.sub.3                                                              nC.sub.5 H.sub.11                                                                   +++ +++ +++ +   +++ ++  ++  ++  ++  +++ ++                 2,4-(Cl).sub.2C.sub.6 H.sub.3                                                              nC.sub.6 H.sub.13                                                                   +++ +++ +++ +   +++ o   ++  ++  +++ +++ +                  2,4-(Cl).sub.2C.sub.6 H.sub.3                                                              nC.sub.7 H.sub.15                                                                   ++  +++ +++ +   +++ o   o   ++  ++  +++ +                  2,4-(Cl).sub.2C.sub.6 H.sub.3                                                              nC.sub.8 H.sub.17                                                                   ++  +++ +++ +   ++  o   o   +   +   ++  +                  2,4-(Cl).sub.2C.sub.6 H.sub.3                                                              ClCH.sub.2                                                                          +++ +++ +++ ++  ++  +   o   +   +++ +++ ++                 __________________________________________________________________________

                                      Tables A6                                   __________________________________________________________________________    ANTIFUNGAL ACTIVITY                                                            ##STR17##                                                                            ANTIFUNGAL ACTIVITY                                                           M. c.                                                                             Ct. m.                                                                            Tr. r.                                                                            Ph. v.                                                                            Cr. n.                                                                            C. tr.                                                                            C. alb.                                                                           Muc.                                                                              A.f.                                                                              Sp. s.                                                                            Sap.                          Alkyl                                                                             isomer                                                                            (1) (2) (3) (4) (5) (6) (7) (8) (9) (10)                                                                              (11)                          __________________________________________________________________________    CH.sub.3                                                                          cis ++  +++ +++ ++  ++  ++  o   o   ++  +   ++                            C.sub.2 H.sub.5                                                                   trans                                                                             ++  +++ ++  +   +   o   o   o   +   +   +                             nC.sub.3 H.sub.7                                                                  cis ++  +++ +++ ++  +++ ++  o   o   ++  ++  ++                            nC.sub.4 H.sub.9                                                                  A + B                                                                             ++  +++ +++ +   ++  +   +   +   +   ++  ++                            nC.sub.5 H.sub.11                                                                 cis ++  +++ +++ +   +++ ++  o   ++  ++  ++  ++                            nC.sub.6 H.sub.13                                                                 cis ++  +++ +++ +   +++ ++  o   +   +   ++  +                             nC.sub.7 H.sub.15                                                                 cis +   +++ +++ +   +++ o   o   +   +   ++  +                             nC.sub.8 H.sub.17                                                                 cis +   +++ +++ +   +++ o   o   +   o   ++  o                             __________________________________________________________________________

                                      Tables A7                                   __________________________________________________________________________    ANTIFUNGAL ACTIVITY                                                            ##STR18##                                                                                  ANTIFUNGAL ACTIVITY                                                           M. c.                                                                             Ct. m.                                                                            Tr. r.                                                                            Ph. v.                                                                            Cr. n.                                                                            C. tr.                                                                            C. alb.                                                                           Muc.                                                                              A.f.                                                                              Sp. s.                                                                            Sap.                    Aryl      isomer                                                                            (1) (2) (3) (4) (5) (6) (7) (8) (9) (10)                                                                              (11)                    __________________________________________________________________________    4-(C.sub.6 H.sub.5)C.sub.6 H.sub.4                                                      cis o   +++ ++  o   ++  o   o   o   o   o   o                       4-(C.sub.6 H.sub.5)C.sub.6 H.sub.4                                                      trans                                                                             o   +++ +   o   o   o   o   o   o   o   o                       4-BrC.sub.6 H.sub.4                                                                     cis +++ +++ +++ +   +++ +   +   +++ ++  ++  ++                      2,4-(Cl).sub.2C.sub.6 H.sub.3                                                           cis +++ +++ +++ o   +++ o   o   +   ++  ++  +                       2,4-(Cl).sub.2C.sub.6 H.sub.3                                                           trans                                                                             +   +++ ++  o   o   o   o   +   o   ++  o                       __________________________________________________________________________

                                      Tables A8                                   __________________________________________________________________________    ANTIFUNGAL ACTIVITY                                                            ##STR19##                                                                              ANTIFUNGAL ACTIVITY                                                           M.c.                                                                              Ct.m.                                                                             Tr.r.                                                                             Ph.v.                                                                             Cr.n.                                                                             C.tr.                                                                             C.alb.                                                                            Muc.                                                                              A.f.                                                                              Sp. s.                                                                            Sap.                        Aryl      (1) (2) (3) (4) (5) (6) (7) (8) (9) (10)                                                                              (11)                        __________________________________________________________________________    C.sub.6 H.sub.5                                                                         +++ +++ +++ +   +++ ++  +   ++  +++ ++  ++                          4-ClC.sub.6 H.sub.4                                                                     +++ +++ +++ +   +++ ++  ++  ++  ++  ++  +                           4-FC.sub.6 H.sub.4                                                                      +++ ++ +                                                                              +++ +   +++ ++  +   +++ ++  ++  ++                          4-CH.sub.3C.sub.6 H.sub.4                                                               +++ +++ +++ +   +++ o   ++  ++  ++  ++  ++                          4-BrC.sub.6 H.sub.4                                                                     +++ +++ +++ +   +++ o   ++  +++ ++  ++  +                           4-OCH.sub.3C.sub.6 H.sub.4                                                              +++ +++ +++ ++  +++ +   o   +++ +++ ++  ++                          4-(C.sub.6 H.sub.5)C.sub.6 H.sub.4                                                      ++  +++ +++ o   +   o   o   o   ++  +   +                           __________________________________________________________________________

                  Table B                                                         ______________________________________                                        ACTIVITY AGAINST PHYCOMYCTES                                                   ##STR20##                                                                    R.sub.1 R.sub.2  Abs.r.   Bas.m. Mort.  Rhi.                                  ______________________________________                                        2,4-(Cl).sub.2                                                                        4-Cl     ++       ++     +      ++                                    4-Br    2-Cl     +        +      +      ++                                    4-Br    4-Br     +++      ++     ++     ++                                    4-CH.sub.3                                                                            4-Cl     ++       +      +      +                                     2,4-(Cl).sub.2                                                                        4-Br     +++      ++     ++     ++                                    4-Cl    4-Br     +++      ++     ++     ++                                    2-Cl    4-Br     ++       ++     +      ++                                    4-Br    4-CH.sub.3                                                                             ++       ++     +      ++                                    4-Cl    4-F      ++       ++     +      +                                     4-Br    4-F      ++       + +    +      ++                                    ______________________________________                                         ##STR21##                                                                    R.sub.1                                                                              R.sub.2   Isomer  Abs.r.                                                                              Bas.m.                                                                              Mort. Rhi.                               ______________________________________                                        4-Cl   4-Cl      B       +++   +     +     +                                  4-Cl   4-F       cis     ++    +     +     +                                  4-Cl   2-CH.sub.3                                                                              A       ++    ++    +     +                                  4-Cl   2,4-(Cl).sub.2                                                                          B       +++   ++    ++    +                                  2,4-(Cl).sub.2                                                                       2-CH.sub.3                                                                              A       +     +     +     +                                  2,4-(Cl).sub.2                                                                       4-Cl      trans   ++    +     ++    +                                  2,4-(Cl).sub.2                                                                       2-CH.sub.3,4-Cl                                                                         A + B   ++    ++    +     +                                  4-Cl   2,6-(Cl).sub.2                                                                          A       ++    +     +     +                                  2,4-(Cl).sub.2                                                                       2-CH.sub.3                                                                              A       ++    ++    +     +                                  2,4-(Cl).sub.2                                                                       4-CH.sub.3                                                                              A       +     ++    +     +                                  2,4-(Cl).sub.2                                                                       4-OCH.sub.3                                                                             A       ++    ++    +     +                                  2,4-(Cl).sub.2                                                                       4-Cl      cis     ++    ++    +     +                                  2,4-(Cl).sub.2                                                                       4-Br      A       +++   ++    ++    ++                                 2,4-(Cl).sub.2                                                                       H         A       ++    ++    +     +                                  2,4-(Cl).sub.2                                                                       3,4-(Cl).sub.2                                                                          A       +++   +++   +     ++                                 2,4-(Cl).sub.2                                                                       3-Cl      A       ++    +++   ++    ++                                 2,4-(Cl).sub.2                                                                       2-Cl      A       +++   ++    +     +                                  2,4-(Cl).sub.2                                                                       2-Br      cis     ++    ++    +     +                                  ______________________________________                                    

                                      Tabble C1                                   __________________________________________________________________________    BACTERIOSTATIC AND BACTERIOCIDAL ACTIVITY                                     The table summarizes the activity against the gram-positive bacteria.          ##STR22##                                                                                bacteriostatic activity                                                                      bacteriocidal activity                             R.sub.1                                                                             R.sub.2                                                                              E. ins.                                                                           Staph.                                                                             Strept.                                                                            E. ins.                                                                            Staph.                                                                             Strept.                                  __________________________________________________________________________    4-Cl  4-Cl  ++   ++   ++   ++   ++   ++                                       4-Cl  H     ++   ++   +++  ++   +    +++                                      4-Cl  2,4-(Cl).sub.2                                                                      +++  ++   +++  ++   ++   +++                                      4-Br  4-Cl  +++  +++  +++  +++  +    +++                                      4-Br  2,4-(Cl).sub.2                                                                      + ++ +    +++  +++  +    +++                                      2,4-(Cl).sub.2                                                                      H     ++   0    ++   ++   0    ++                                       4-OCH.sub.3                                                                         4-Cl  ++   +    ++   +    +    ++                                       H     2,4-(Cl).sub.2                                                                      ++   ++   +++  +    +    ++                                       2,4-(Cl).sub.2                                                                      4-Cl  +++  ++   +++  ++   +    ++                                       H     4-Cl  +++  +    +++  +    +    ++                                       4-Cl  2-Cl  +++  ++   +++  ++   +    ++                                       2-Cl  2,4-(Cl).sub.2                                                                      +++  ++   +++  ++   +    +++                                      4-Br  2-Cl  +++  +    ++   +++  +    ++                                       2-Cl  4-Cl  +++  +    +++  +++  +    +++                                      2,4-(Cl).sub.2                                                                      2,4-(Cl).sub.2                                                                      +++  ++   +++  +++  +    +++                                      4-Br  H     ++   +    +++  ++   +    +++                                      H     4-Br  +++  0    +++  +++  0    +++                                      4-CH.sub.3                                                                          2,4-(Cl).sub.2                                                                      +++  +++  +++  +++  ++   +++                                      4-Br  4-Br  +++  ++   +++  +++  +    +++                                      2,4-(Cl).sub.2                                                                      2-Cl  +++  +++  +++  +++  ++   +++                                      4-CH.sub.3                                                                          4-Cl  +++  ++   +++  +++  +    +++                                      2,4-(Cl).sub.2                                                                      4-Br  +++  ++   +++  ++   +    ++                                       4-Cl  4-Br  +++  ++   +++  +++  ++   +++                                      4-CH.sub.3                                                                          4-Br  +++  ++   +++  +++  +    +++                                      3-Cl  2,4-(Cl).sub.2                                                                      ++   +    +++  ++   +    +++                                      2-Cl  4-Br  ++   ++   ++   ++   +    ++                                       4-CH.sub.3                                                                          2-Cl  +++  +    +++  ++   +    +++                                      4-Cl  4-CH.sub.3                                                                          +++  +    +++  ++   +    +++                                      4-Br  4-CH.sub.3                                                                          +++  ++   ++   ++   +    ++                                       4-Cl  4-F   +    0    ++   +    0    ++                                       4-Br  4-F   ++   +    +++  ++   +    +++                                      __________________________________________________________________________

                                      table C2                                    __________________________________________________________________________    BACTERIOSTATIC AND BACTERIOCIDAL ACTIVITY                                      ##STR23##                                                                                     bacteriostatic activity                                                                     bacteriocidal activity                         R.sub.1                                                                            R.sub.2 Isomer                                                                             E. ins.                                                                           Staph.                                                                            Strept.                                                                            E. ins.                                                                            Staph.                                                                            Strept.                               __________________________________________________________________________    4-Cl 2-CH.sub.3,4-Cl                                                                       cis ++++ 0   ++++ ++++ 0   ++++                                  4-Cl 4-CH.sub.3                                                                            trans                                                                             +++  ++  +++  +++  +   +++                                   4-Cl 2-CH.sub.3,4-Cl                                                                       trans                                                                             ++++ ++  ++++ ++++ +   +++                                   4-Cl 4-CH.sub.3                                                                            cis +++  ++  +++  +++  +   +++                                   4-Cl 4-Cl    A   ++++ +   +++  ++++ +   +++                                   4-Cl 4-Cl    B   ++++ ++  +++  ++++ +   +++                                   4-Cl 2,4-(Cl).sub.2                                                                        A   0    0   ++   0    0   ++                                    4-Cl 4-F     cis +++  0   +++  +++  0   +++                                   4-Cl 2-CH.sub.3                                                                            A   ++++ ++  ++++ ++++ +   ++++                                  4-Cl 2-Cl    A   +++  0   +++  +++  0   +++                                   4-Cl 2-CH.sub.3                                                                            B   ++++ ++  +++  +++  +   +++                                   4-Cl 2,4-(Cl).sub.2                                                                        B   ++++ ++  ++++ ++++ ++  ++++                                  4-Cl 4-OCH.sub.3                                                                           A   +++  0   +++  ++   0   +++                                   4-Cl 4-F     trans                                                                             ++   +   ++   +    +   ++                                    4-Cl 4-OCH.sub.3                                                                           B   ++   +   ++   +    +   ++                                    4-Cl 2,6-(Cl).sub.2                                                                        A   +++  0   ++++ ++   0   ++++                                  4-Cl 2-Cl    B   +++  +   ++   +++  +   ++                                    4-Cl 2,6-(Cl).sub.2                                                                        B   +++  ++  +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     4-CH.sub.3                                                                            B   ++   ++  ++   ++   +   ++                                    2,4-(Cl).sub.2                                                                     4-F     A   ++   ++  ++   ++   0   ++                                    2,4-(Cl).sub.2                                                                     2-CH.sub.3                                                                            A   +++  +   +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     4-CH.sub.3                                                                            A   +++  ++  +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     4-OCH.sub.3                                                                           A   ++   +   ++   ++   +   ++                                    2,4-(Cl).sub.2                                                                     4-Cl    cis ++   +   ++   ++   +   ++                                    2,4-(Cl).sub.2                                                                     2-CH.sub.3                                                                            B   +++  +   +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     2,4-(Cl).sub.2                                                                        A   +++  0   +++  +++  0   +++                                   2,4-(Cl).sub.2                                                                     4-Cl    trans                                                                             +++  ++  +++  +++  ++  +++                                   2,4-(Cl).sub.2                                                                     4-Br    A   +++  +   +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     2,4-(Cl).sub.2                                                                        B   +++  ++  +++  ++   +   +++                                   2,4-(Cl).sub.2                                                                     H       A   +++  +   +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     3,4-(Cl).sub.2                                                                        A   +++  ++  +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     3-Cl    A   +++  ++  +++  +++  ++  +++                                   2,4-(Cl).sub.2                                                                     2-Cl    A   +++  ++  +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     2-CH.sub.3,4-Cl                                                                       A + B                                                                             +++  ++  +++  ++   +   +++                                   2,4-(Cl).sub.2                                                                     2-Cl    B   +++  +   +++  ++   +   +++                                   2,4-(Cl).sub.2                                                                     2,6-(Cl).sub.2                                                                        A   +++  ++  +++  ++   +   ++                                    2,4-(Cl).sub.2                                                                     3,5-(CH.sub.3).sub.2,4-Cl                                                             A   +++  0   +++  +++  0   +++                                   2,4-(Cl).sub.2                                                                     2,4-(Br).sub.2                                                                        A   ++ + 0   +++  +++  0   +++                                   2,4-(Cl).sub.2                                                                     4-CN    A   +++  +   ++   0    0   ++                                    2,4-(Cl).sub.2                                                                     2-Br    cis +++  ++  +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     2-OCH.sub.3                                                                           A   +++  +   +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     2-Br    trans                                                                             +++  ++  ++   ++   +   ++                                    2,4-(Cl).sub.2                                                                     2,4,6-(Cl).sub.3                                                                      A   +++  0   +++  ++   0   ++                                    2,4-(Cl).sub.2                                                                     2,5-(CH.sub.3).sub.2                                                                  A   +++  ++  +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     2,5-(CH.sub.3).sub.2                                                                  B   +++  ++  +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     2-Cl,4-tert.but.                                                                      A   +++  ++  +++  ++   0   ++                                    2,4-(Cl).sub.2                                                                     2,4,5-(Cl).sub.3                                                                      A   ++++ 0   ++   +++  0   ++                                    2,4-(Cl).sub.2                                                                     2-Cl,4-tert.but.                                                                      B   ++++ ++  ++++ +++  +   +++                                   2,4-(Cl).sub.2                                                                     2,4,5-(Cl).sub.3                                                                      B   +++  +   +++  ++   +   ++                                    2,4-(Cl).sub.2                                                                     2,5-(Br).sub.2,4-CH.sub.3                                                             A   +++  +   +++  ++   +   ++                                    2,4-(Cl).sub.2                                                                     2-F     A   +++  +   ++++ ++   +   +++                                   4-CH.sub.3                                                                         4-Br    A   +++  ++  ++++ ++   +   +++                                   4-Cl 4-Br    A   ++++ ++  ++++ +++  +   +++                                   4-Br 4-Br    A   ++++ +   ++++ +++  +   ++ +                                  2,4-(Cl).sub.2                                                                     2-OC.sub.2 H.sub.5                                                                    A   ++++ 0   ++++ +++  0   +++                                   2-Cl 4-Br    A + B                                                                             ++++ ++  ++++ +++  +   +++                                   2-Cl 4-Br    B   +++  ++  ++++ ++   +   +++                                   H    4-Br    A   +++  ++  ++++ +    0   +++                                   2-Br 4-Br    A   ++++ +++ ++++ +++  ++  +++                                   2-Br 4-Br    B   ++++ ++  ++++ +++  +   ++++                                  2,4-(Cl).sub.2                                                                     4-C.sub.6 H.sub.5                                                                     A + B                                                                             ++++ 0   ++   +++  0   ++                                    2,4-(Cl).sub.2                                                                     4-C.sub.6 H.sub.5                                                                     B   0    0   ++++ 0    0   +++                                   2,4-(Cl).sub.2                                                                     2,6-(CH.sub.3).sub.2                                                                  A   ++++ ++  ++++ +++  ++  +++                                   2,4-(Cl).sub.2                                                                     4-Br    B   +++  +++ +++  ++   +   ++                                    2,4-(Cl).sub.2                                                                     2,6-(CH.sub.3).sub.2                                                                  A + B                                                                             +++  ++  +++  ++   +   ++                                    2,4-(Cl).sub.2                                                                     3,5-(CH.sub.3).sub.2                                                                  A   +++  ++  +++  +++  +   +++                                   2,4-(Cl).sub.2                                                                     4-iC.sub.3 H.sub.7                                                                    A + B                                                                             ++   ++  +++  ++   +   ++                                    2,4-(Cl).sub.2                                                                     2-Cl,6-CH.sub.3                                                                       A   ++   ++  ++   ++   +   ++                                    2,4-(Cl).sub.2                                                                     4-tert.but.                                                                           A   +++  ++  ++   ++   +   ++                                    2,4-(Cl).sub.2                                                                     3,5-(Cl).sub.2                                                                        A   ++   ++ +                                                                              ++++ ++   ++  +++                                   2,4-(Cl).sub.2                                                                     3-CH.sub.3, 4-Cl                                                                      A   +++  ++  ++   ++   ++  +                                     __________________________________________________________________________

                                      table C3                                    __________________________________________________________________________    BACTERIOSTATIC AND BACTERIOCIDAL ACTIVITY                                      ##STR24##                                                                                   Bacteriostatic activity                                                                      Bacteriocidal activity                          R.sub.1                                                                            R.sub.2                                                                            Isomer                                                                              E. ins.                                                                           Staph.                                                                             Strept.                                                                            E. ins.                                                                            Staph.                                                                             Strept.                               __________________________________________________________________________    2,4-(Cl).sub.2                                                                     4-Br A + B                                                                              +++  ++   ++++ ++   +    +++                                   2,4-(Cl).sub.2                                                                     H    A + B                                                                              ++++ ++   ++++ +++  +    +++                                   __________________________________________________________________________

                                      table C4                                    __________________________________________________________________________     ##STR25##                                                                                   Bacteriostatic activity                                                                      bacteriocidal activity                          R.sub.1                                                                            R.sub.2                                                                            Isomer                                                                              E. ins.                                                                           Staph.                                                                             Strept.                                                                            E. ins.                                                                            Staph.                                                                             Strept.                               __________________________________________________________________________    2,4-(Cl).sub.2                                                                     2-Cl      ++++ +++  ++++ +++  ++   +++                                   2,4-(Cl).sub.2                                                                     2,4-(Cl).sub.2                                                                          ++++ +++  ++++ +++  ++   +++                                   2,4-(Cl).sub.2                                                                     2,6-(Cl).sub.2                                                                     A + B                                                                              ++++ +++  ++++ +++  ++   +++                                   2,4-(Cl).sub.2                                                                     4-OCH.sub. 3                                                                       A + B                                                                              ++++ +    +++  +++  +    ++                                    2,4-(Cl).sub.2                                                                     4-Cl      ++++ ++   ++++ +++  +    +++                                   2,4-(Cl).sub.2                                                                     H         ++++ ++   +++  +++  0    ++                                    __________________________________________________________________________

                                      table C5                                    __________________________________________________________________________    BACTERIOSTATIC AND BACTERIOCIDAL ACTIVITY                                      ##STR26##                                                                                         Bacteriostatic activity                                                                      Bacteriocidal activity                    Ar         R    isomer                                                                             E. ins.                                                                            Staph.                                                                             Strept.                                                                            E. ins.                                                                            Staph.                                                                             Strept.                         __________________________________________________________________________    2,4-(Cl).sub.2C.sub.6 H.sub.3                                                            C.sub.2 H.sub.5                                                                    A + B                                                                              +++  ++   +++  ++   0    +++                             2-ClC.sub.6 H.sub.4                                                                      C.sub.2 H.sub.5                                                                    A + B                                                                              ++   +    o    ++   +    o                               2-CH.sub.3C.sub.6 H.sub.4                                                                C.sub.2 H.sub.5                                                                    A + B                                                                              ++   o    ++   o    o    o                               4-CH.sub.3C.sub.6 H.sub.4                                                                C.sub.2 H.sub.5                                                                    A + B                                                                              ++   +    ++   ++   o    ++                              2,3,4-(Cl).sub. 3C.sub.6 H.sub.2                                                         C.sub.2 H.sub.5                                                                    A + B                                                                              +++  ++   +++  +++  +    +++                             2-BrC.sub.6 H.sub.4                                                                      C.sub.2 H.sub.5                                                                    A + B                                                                              ++   +    ++   ++   o    ++                              2,3-(Cl).sub.2C.sub.6 H.sub.3                                                            C.sub.2 H.sub.5                                                                    A + B                                                                              ++   +    ++   ++   o    ++                              2-Cl,4-FC.sub.6 H.sub.3                                                                  C.sub.2 H.sub.5                                                                    A + B                                                                              ++   o    ++   ++   o    ++                              4-BrC.sub.6 H.sub.4                                                                      C.sub.2 H.sub.5                                                                    A + B                                                                              ++   o    +    ++   o    +                               3-ClC.sub.6 H.sub.4                                                                      C.sub.2 H.sub.5                                                                    A + B                                                                              ++   o    ++   ++   o    ++                              2-Cl,4-BrC.sub.5 H.sub.3                                                                 C.sub.2 H.sub.5                                                                    A + B                                                                              +++  +    ++   +++  +    + +                             2,4-(Br).sub.2C.sub.6 H.sub.3                                                            C.sub.2 H.sub.5                                                                    A + B                                                                              +++  +    ++   +++  +    ++                              4-OCH.sub.3C.sub.6 H.sub.4                                                               C.sub.2 H.sub.5                                                                    A + B                                                                              +    o    +    +    o    +                               2-thienyl  C.sub.2 H.sub.2                                                                    A + B                                                                              +    o    +    o    o    +                               2-CH.sub.3,4-ClC.sub.6 H.sub.3                                                           C.sub.2 H.sub.5                                                                    A + B                                                                              +++  +    +    +++  +    +                               2-Cl, 4-OCH.sub.3                                                                        C.sub.2 H.sub.5                                                                    A + B                                                                              ++   +    ++   +    o    +                               2-naphthyl C.sub.2 H.sub.5                                                                    A + B                                                                              +++  +    ++   +    o    +                               5-Cl-2-thienyl                                                                           C.sub.2 H.sub.5                                                                    A + B                                                                              ++   +    ++   o    o    o                               2-OCH.sub.3,4-ClC.sub.6 H.sub.3                                                          C.sub.2 H.sub.5                                                                    A + B                                                                              +    o    +    +    o    +                               2,4-(Cl).sub.2C.sub.6 H.sub.3                                                            nC.sub.3 H.sub.7                                                                   A + B                                                                              +++  ++   +++  +++  +    +++                             2,4-(Cl).sub.2C.sub.6 H.sub.3                                                            nC.sub.4 H.sub.9                                                                   A + B                                                                              +++  +++  +++  +++  +++  +++                             2,4-(Cl).sub.2C.sub.6 H.sub.3                                                            nC.sub.5 H.sub.11                                                                  A + B                                                                              +++  ++   +++  +++  ++   +++                             2,4-(Cl).sub.2C.sub.6 H.sub.3                                                            nC.sub.6 H.sub.13                                                                  A + B                                                                              +++  +++  +++  +++  ++   +++                             2,4-(Cl).sub.2C.sub.6 H.sub.3                                                            nC.sub.7 H.sub.15                                                                  A + B                                                                              +++  +++  +++  +++  ++   +++                             2,4-(Cl).sub.2C.sub.6 H.sub.3                                                            nC.sub.8 H.sub.17                                                                  A + B                                                                              +++  ++   +++  +++  ++   +++                             2,4-(Cl).sub.2C.sub.6 H.sub.3                                                            CH.sub.2 Cl                                                                        A + B                                                                              +    o    +    +    o    +                               2,4-(Cl).sub.2C.sub.6 H.sub.3                                                            CH.sub.2 OH                                                                        trans                                                                              +    o    +    o    o    +                               2,4-(Cl).sub.2C.sub.6 H.sub.3                                                            CH.sub.2 OH                                                                        A + B                                                                              ++   o    +    ++   o    +                               2,4-(Cl).sub.2C.sub.6 H.sub.3                                                            CH.sub.2 OH                                                                        cis  +    o    o    +    o    o                               3,4,5-(Cl).sub.3C.sub.6 H.sub.2                                                          C.sub.2 H.sub.5                                                                    A + B                                                                              +++  ++   +++  ++   +    ++                              __________________________________________________________________________

                                      table C6                                    __________________________________________________________________________    BACTERIOSTATIC AND BACTERIOCIDAL ACTIVITY                                      ##STR27##                                                                                  Bacteriostatic activity                                                                      Bacteriocidal activity                           Alkyl    isomer                                                                             E. ins.                                                                            Staph.                                                                             Strept.                                                                            E. ins.                                                                            Staph.                                                                             Strept.                                __________________________________________________________________________    CH.sub.3 cis  +    o    o    +    o    o                                      C.sub.2 H.sub.5                                                                        trans                                                                              ++   +    ++   +    o    +                                      nC.sub.3 H.sub.7                                                                       cis  ++   +    +    ++   o    o                                      nC.sub.4 H.sub.9                                                                       A + B                                                                              +++  ++   +++  +    o    +                                      nC.sub.5 H.sub.11                                                                      cis  +++  +++  +++  +++  o    ++                                     nc.sub.6 H.sub.13                                                                      cis  +++  ++   ++   ++   +    ++                                     nC.sub.7 H.sub.15                                                                      cis  +++  +++  +++  +++  +    ++                                     nC.sub.8 H.sub.17                                                                      cis  +++  ++   +++  ++   +    +++                                    __________________________________________________________________________

                                      Table C7                                    __________________________________________________________________________     ##STR28##                                                                                  Bacteriostatic activity                                                                      Bacteriocidal activity                           Aryl     isomer                                                                             E. ins.                                                                            Staph.                                                                             Strept.                                                                            E. ins.                                                                            Staph.                                                                             Strept.                                __________________________________________________________________________    4-(C.sub.6 H.sub.5)C.sub.6 H.sub.4                                                     cis  +++  +++  +++  +++  +    +++                                    4-(C.sub.6 H.sub.5)C.sub.6 H.sub.4                                                     trans                                                                              +++  ++   +++  +++  ++   +++                                    4-BrC.sub.6 H.sub.4                                                                    cis  +++  ++   +++  +++  +    +++                                    2,4-(Cl).sub.2c.sub.6 H.sub.3                                                          cis  +++  +++  +++  ++   +    ++                                     2,4-(Cl).sub.2C.sub.6 H.sub.3                                                          trans                                                                              +++  ++   +++  +++  +    ++                                     __________________________________________________________________________

                                      Table C8                                    __________________________________________________________________________    BACTERIOSTATIC AND BACTERIOCIDAL ACTIVITY                                      ##STR29##                                                                              Bacteriostatic activity                                                                      Bacteriocidal activity                               Aryl      E. ins.                                                                            Staph.                                                                             Strept.                                                                            E. ins.                                                                            Staph.                                                                             Strept.                                    __________________________________________________________________________    C.sub.6 H.sub.5                                                                         +++  ++   ++   +++  +    ++                                         4-ClC.sub.6 H.sub.4                                                                     +++  ++   ++   +++   ++  ++                                         4-FC.sub.6 H.sub.4                                                                      +++  ++   ++   ++   +    ++                                         4-CH.sub.3C.sub.6 H.sub.4                                                               +++  ++   +++  +++   ++   +++                                       4-BrC.sub.6 H.sub.4                                                                     +++  ++   +++  +++   ++   +++                                       4-OCH.sub.3C.sub.6 H.sub.4                                                              +++  +    +++  +++  +     +++                                       4-(C.sub.6 H.sub.5)C.sub.6 H.sub.4                                                      +++  ++   +++  ++   +    ++                                         __________________________________________________________________________

in view of the aforementioned antifungal and antibacterial activitiesthis invention provides valuable compositions comprising the subject1,3-dioxolan-2-ylmethyl imidazoles (I) or the acid addition saltsthereof as the active ingredient in a solvent or a solid, semi-solid orliquid diluent or carrier, and, in addition, it provides an effectivemethod of combatting fungus or bacterial growth by use of an effectiveanti-fungal or anti-bacterial amount of such ketals (I) or saltsthereof. The subject compounds can be used in suitable solvents ordiluents, in the form of emulsions, suspensions, dispersions orointments, on suitable solid or semisolid carrier substances, inordinary or synthetic soaps, detergents or dispersion media, if desired,together with other compounds having arachnicidal, insecticidal,ovicidal, fungicidal and/or bactericidal effects, or together withinactive additives.

Solid carrier substances which are suitable for the preparation ofcompositions in powder form include various inert, porous and pulverousdistributing agents of inorganic or organic nature, such as, forexample, tricalcium phosphate, calcium carbonate, in the form ofprepared chalk or ground limestone, kaolin, bole, bentonite, talcum,kieselguhr and boric acid; powdered cork, sawdust, and other finepulverous materials of vegetable origin are also suitable carriersubstances.

The active ingredient is mixed with these carrier substances, forexample, by being ground therewith; alternatively, the inert carriersubstance is impregnated with a solution of the active component in areadily volatile solvent and the solvent is thereafter eliminated byheating or by filtering with suction at reduced pressure. By addingwetting and/or dispersing agents, such pulverous preparations can alsobe made readily wettable with water, so that suspensions are obtained.

Inert solvents used for the production of liquid preparations shouldpreferably not be readily inflammable and should be as far as possibleodorless and as far as possible non-toxic to warm-blooded animals orplants in the relevant surroundings. Solvents suitable for this purposeare high-boiling oils, for example, of vegetable origin, andlower-boiling solvents with a flash point of at least 30° C., such as,for example, polyethylene glycols, isopropanol, dimethylsulfoxide,hydrogenated naphthalenes and alkylated naphthalenes. It is, of cours,also possible to use mixtures of solvents. Solutions can be prepared inthe usual way, if necessary, with assistance of solution promotors.Other liquid forms which can be used consist of emulsions or suspensionsof the active compound in water or suitable inert solvents, or alsoconcentrates for preparing such emulsions, which can be directlyadjusted to the required concentration. For this purpose, the activeingredient is, for example, mixed with a dispersing or emulsifyingagent. The active component can also be dissolved or dispersed in asuitable inert solvent and mixed simultaneously or subsequently with adispersing or emulsifying agent.

It is also possible to use semi-solid carrier substances of a creamointment, paste or waxlike nature, into which the active component canbe incorporated, if necessary, with the aid of solution promotors and/oremulsifiers. Vaseline and other cream bases are examples of semi-solidcarrier substances.

Furthermore, it is possible for the active component to be used in theform of aerosols. For this purpose, the active component is dissolved ordispersed, if necessary, with the aid of suitable inert solvents ascarrier liquids, such as difluorodichloromethane, which at atmosphericpressure boils at a temperature lower than room temperature, or in othervolatile solvents. In this way, solutions under pressure are obtainedwhich, when sprayed, yield aerosols which are particularly suitable forcontrolling or combatting fungi and bacteria, e.g., in closed chambersand storage rooms, and for application to vegetation for eradicating orfor preventing infections by fungi or bacteria.

The subject compounds and compositions thereof can be applied byconventional methods. For example, a fungus or bacterial growth or amaterial to be treated or to be protected against attack by fungus orbacterium can be treated with the subject compounds and the compositionsthereof by dusting, sprinkling, spraying, brushing, dipping, smearing,impregnating or other suitable means.

When the subject compounds are employed in combination with suitablecarriers, e.g., in solution, suspension, dust, powder, ointment,emulsion, and the like forms, a high activity over a very high range ofdilution is observed. For example, concentrations of the activeingredient ranging from 0.1-10 percent by weight, based on the weight ofcomposition employed, have been found effective in combatting fungi orbacteria. Of course, higher concentrations may also be employed aswarranted by the particular situation.

The following examples are intended to illustrate, but not to limit, thescope of the present invention. Unless otherwise stated, all parts areby weight.

A. novel intermediates

example i

a mixture of 11.7 parts of 2-bromo-4'-chloroacetophenone, 9 parts of1-(p-chlorophenyl)-1,2-ethanediol, 0.5 parts of p-toluenesulfonic acidand 80 parts of benzene is stirred and refluxed for 2 days withwater-separator. The reaction mixture is cooled and washed successivelytwice with a sodium hydrogen carbonate solution and once with water. Theorganic phase is dried and evaporated. The residue is triturated inpetroleum ether and cooled on ice. The precipitated product is filteredoff, crystallized from methanol, stirred in acetonitrile while coolingon ice, filtered off again and washed once more with acetonitrile,yielding 2-(bromomethyl)-2,4-bis(p-chlorophenyl)-1,3-dioxolane.

EXAMPLE II

A mixture of 11.6 parts of 2-bromo-4'-chloroacetophenone, 8.4 parts ofα-(hydroxymethyl)benzylalcohol, 0.1 parts of p-toluene sulfonic acid,210 parts of benzene and 40 parts of ethanol is stirred and refluxed for24 hours. The reaction mixture is evaporated and the residue istriturated in methanol. The product is filtered off and crystallizedfrom methanol, yielding2-(bromomethyl)-2-(p-chlorophenyl)-4-phenyl-1,3-dioxolane; mp. 60° C.

EXAMPLE III

A mixture of 11.6 parts of 2-bromo-4'-chloroacetophenone, 12.4 parts of1-(2,4-dichlorophenyl)-1,2-ethanediol, 0.1 parts of p-toluenesulfonicacid, 80 parts of n-butanol and 160 parts of benzene is stirred andrefluxed for 24 hours with water-separator. The solvent is removed invacuo and the residue is triturated in methanol. The precipitatedproduct is filtered off and crystallized from petroleum ether, yielding2-(bromomethyl)-2-(p-chlorophenyl)-4-(2,4-dichlorophenyl)-1,3-dioxolane;m.p. 82.7° C.

EXAMPLE IV

Following the procedure of Example III and using equivalent amounts ofthe appropriate starting materials, the following dioxolanes areprepared:

    ______________________________________                                         ##STR30##                                                                    R.sub.6      R.sub.7     Melting Point                                        ______________________________________                                        4-Br         4-Cl         101.3°                                       4-Br         2,4-(Cl).sub.2                                                                              99.9°                                       4-OCH.sub.3  4-Cl         115.6°                                        --          4-Cl          63.9°                                       4-CH.sub.3   2,4-(Cl).sub.2                                                                              89.9°                                       4-Br         4-Br          96.8°                                       4-CH.sub.3   4-Cl         122°                                         4-CH.sub.3   4-Br         118.6°                                       4-CH.sub.3   2-Cl                                                             ______________________________________                                    

EXAMPLE V

A mixture of 13.4 parts of 2-bromo-2',4'-dichloroacetophenone, 8.4 partsof α-(hydroxymethyl)benzyl alcohol, 1.15 parts of p-toluenesulfonicacid, 160 parts of benzene and 140 parts of n-butanol is stirred andrefluxed for 48 hours with a water-separator. The solvent is removed invacuo. The residue is purified by column-chromatography over silica gel,using chloroform as eluent. The pure fractions are collected and theeluent is evaporated, yielding2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-phenyl-1,3-dioxolane asresidue.

EXAMPLE VI

Following the procedure of Example V but substituting for theα-(hydroxymethyl)benzyl alcohol used therein equivalent amounts of2,4-dichloro-α-(hydroxymethyl)benzyl alcohol andp-chloro-α-(hydroxymethyl)benzyl alcohol, and using the appropriatelysubstituted 2-bromoacetophenone, there are prepared(2-(bromomethyl)-4-(2,4-dichlorophenyl)-2-phenyl-1,3-dioxolane and2-(bromomethyl)-4-(p-chlorophenyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane.

EXAMPLE VII

A mixture of 11.5 parts of 2-bromo-p-chloroacetophenone, 10.4 parts ofo-chloro-α-(hydroxymethyl)benzylalcohol, 0.2 parts of p-toluenesulfonicacid, 180 parts of benzene and 80 parts of butanol is stirred andrefluxed overnight with water-separator. The solvent is removed in vacuoand the residue is dissolved in chloroform. The chloroform solution isstirred with silica gel for 30 minutes. The silica gel is filtered offand the solvent is removed in vacuo, yielding2-(bromomethyl)-4-(o-chlorophenyl)-2-(p-chlorophenyl)-1,3-dioxolane as aresidue.

EXAMPLE VIII

Following the procedure of Example VII and using equivalent amounts ofthe appropriate starting materials, the following dioxolanes areprepared:

    ______________________________________                                         ##STR31##                                                                    R.sub.6      R.sub.7     Melting Point                                        ______________________________________                                        2-Cl         2,4-(Cl).sub.2                                                   4-Br         2-Cl                                                             2-Cl         4-Cl                                                             2,4-(Cl).sub.2                                                                             2,4-(Cl).sub.2                                                   4-Br          --         70°                                            --          4-Br        71.3°                                         2,4-(Cl).sub.2                                                                             2-Cl                                                             2,4-(Cl).sub.2                                                                             4-Br                                                             4-Cl         4-Br        80.5°                                         3-Cl         2,4-(Cl).sub.2                                                   2-Cl         4-Br                                                             4-Cl         4-CH.sub.3                                                       4-Br         4-CH.sub.3                                                       4-Cl         4-F                                                              4-Br         4-F                                                              ______________________________________                                    

example ix

a mixture of 11.7 parts of 2-bromo-4'-chloroacetophenone, 11.9 parts of1-(4-chloro-o-tolyloxy)-2,3-propanediol, 2.5 parts of p-toluenesulfonicacid and 240 parts of benzene is stirred and refluxed for 24 hours in afour-necked round-bottomed flask equipped with a watertrap. The benzenesolution is washed successively with a diluted sodium hydroxide solutionand with water. The solvent is removed in vacuo. The residue iscrystallized from methanol and the less pure fraction is recrystallizedfrom diisopropylether, yieldingA-2-(bromomethyl)-2-(p-chlorophenyl)-4-(4-chloro-o-tolyloxymethyl)-1,3-dioxolane;m.p. 102.5° C. The methanol filtrate is evaporated in vacuo, yieldingB-2-(bromomethyl)-2-(p-chlorophenyl)-4-(4-chloro-o-tolyloxymethyl)-1,3-dioxolaneas a residue.

EXAMPLE X

Following the procedure of Example IX and using equivalent amounts ofthe appropriate starting materials, the following dioxolanes areprepared:

    ______________________________________                                         ##STR32##                                                                    Isomer   R.sub.6     R.sub.7    Melting Point                                 ______________________________________                                        A        4-Cl        4-CH.sub.3                                               B        4-Cl        4-CH.sub.3                                               A        4-Cl        2,4-Cl                                                   B        4-Cl        2,4-Cl                                                   A        4-Cl        4-F        102°                                   B        4-Cl        4-F                                                      A        4-Cl        2-CH.sub.3 82.2 - 85°                             B        4-Cl        2-CH.sub.3                                               A        4-Cl        2-Cl       85 - 88.6°                             B        4-Cl        2-Cl                                                     A        4-Cl        4-OCH.sub.3                                              B        4-Cl        4-OCH.sub.3                                              A        2,4-(Cl).sub.2                                                                            4-F                                                      A        2,4-(Cl).sub.2                                                                            4-OCH.sub.3                                              ______________________________________                                    

example xi

a mixture of 11.7 parts of 2-bromo-4'-chloroacetophenone, 12.2 parts of1-(p-chlorophenoxy)-2,3-propanediol, 3 parts of p-toluenesulfonic acidand 240 parts of benzene is stirred and refluxed for 20 hours in afour-necked round-bottom flask equipped with a watertrap. The benzenesolution is washed successively with a diluted sodium hydroxide solutionand with water. The solvent is removed in vacuo. The residue istriturated in methanol. The precipitated product is filtered off(methanol filtrate is set aside) and crystallized from toluene, yieldingA-2-(bromomethyl)-4-(p-chlorophenoxymethyl)-2-(p-chlorophenyl)-1,3-dioxolane;m.p. 165° C.

The methanol filtrate is evaporated in vacuo. The residue ischromatographed over silica gel with chloroform as eluent, yieldingB-2-(bromomethyl)-4-(p-chlorophenoxymethyl)-2-(p-chlorophenyl)-1,3-dioxolaneas a residue.

EXAMPLE XII

A mixture of 13.4 parts of 2-bromo-2',4'-dichloroacetophenone, 11.2parts of 1-(p-tolyloxy)-2,3-propanediol, 3 parts of p-toluenesulfonicacid and 240 parts of benzene is stirred and refluxed in a four-neckedround-bottomed flask, equipped with a water-trap. When no more water isevolved (20 hours), the benzene solution is washed successively withdiluted sodium hydroxide solution and twice with water. The solution isdried and the solvent is removed in vacuo. The residue is triturated inmethanol. The precipitated product is filtered off (filtrate is setaside) and crystallized from butanol, yieldingA-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(p-tolyloxymethyl)-1,3-dioxolane.

The methanol filtrate (see above) is evaporated in vacuo and residue isdissolved in chloroform. This solution is stirred with silica gel for 5hours. The mixture is filtered and the filtrate is evaporated in vacuo,yieldingB-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(p-tolyloxymethyl)-1,3-dioxolane.

EXAMPLE XIII

Following the procedure of Example XII and using equivalent amounts ofthe appropriate starting materials, the following dioxolanes areprepared:

    ______________________________________                                         ##STR33##                                                                    Isomer R.sub.6    R.sub.7       Melting Point                                 ______________________________________                                        A      2,4-(Cl).sub.2                                                                           4-Cl                                                        B      2,4-(Cl).sub.2                                                                           4-Cl                                                        A      2,4-(Cl).sub.2                                                                           2,4-(Cl).sub.2                                              B      2,4-(Cl).sub.2                                                                           2,4-(Cl).sub.2                                              A      2,4-(Cl).sub.2                                                                            --            97.6°                                 A      2,4-(Cl).sub.2                                                                           3,4-(Cl).sub.2                                              A      2,4-(Cl).sub.2                                                                           3-Cl                                                        A      2,4-(Cl).sub.2                                                                           4-Cl,3,5-(CH.sub.3).sub.2                                                                   115.8°                                 A      2,4-(Cl).sub.2                                                                           2,4-(Br).sub.2                                              A      2,4-(Cl).sub.2                                                                           4-CN                                                        A      2,4-(Cl).sub.2                                                                           2-OCH.sub.3                                                 A + B  2,4-(Cl).sub.2                                                                           4-C.sub.6 H.sub.5                                           A + B  2,4-(Cl).sub.2                                                                           4-iC.sub.3 H.sub.7                                                                          90°                                    A      2,4-(Cl).sub.2                                                                           4-Cl,3-CH.sub.3                                             A      2,4-(Cl).sub.2                                                                           3,5-(Cl).sub.2                                              A      2,4-(Cl).sub.2                                                                           4-tert.butyl                                                ______________________________________                                    

EXAMPLE XIV

A mixture of 11.7 parts of 2-bromo-4'-chloroacetophenone, 14.2 parts of1-(2,6-dichlorophenoxy)-2,3-propanediol, and 3 parts ofp-toluenesulfonic acid and 240 parts of benzene is stirred and refluxedfor 20 hours in a four-necked round-bottomed flask equipped withwatertrap. The benzene-solution is washed successively with a dilutedsodium hydroxide solution and with water. The solvent is removed invacuo, yielding A +B-2-(bromomethyl)-2-(p-chlorophenyl)-4-(2,6-dichlorophenoxymethyl)-1,3-dioxolaneas a residue.

EXAMPLE XV

A mixture of 13.4 parts of 2-bromo-2',4'-dichloroacetophenone, 11.2parts of 3-(o-tolyloxy)-1,2-propanediol, 3 parts of p-toluenesulfonicacid and 240 parts of benzene is stirred and refluxed in a four-neckedround bottomed flask equipped with a water-trap. After 20 hours, thetheoretical amount of water is evolved and the reaction mixture isallowed to cool to room temperature. The mixture is washed successivelywith diluted sodium hydroxide solution and twice with water. The solventis removed in vacuo and the residue is dissolved in chloroform. Thissolution is stirred with silica gel, filtered and the filtrate isevaporated in vacuo, yielding A +B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(o-tolyloxymethyl)-1,3-dioxolane.

EXAMPLE XVI

Following the procedure of Example XV but substituting for the3-(o-tolyloxy)-1,2-propanediol used therein equivalent amounts of theappropriate starting material, the following dioxolanes are prepared:A + B2-(bromomethyl)-4-(o-chlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane;2-(bromomethyl)-4-(2,6-dichlorophenoxymethyl-2-(2,4-dichlorophenyl)-1,3-dioxolane;A + B2-(bromomethyl)-4-(o-bromophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane;A + B2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(2-bromophenyl)-1,3-dioxolane;A + B2-(bromomethyl)-4-(2-chloro-6-methylphenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane;and A + B2-(bromomethyl)-4-(2,3-dichlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane.

EXAMPLE XVII

A mixture of 6 parts of 2-bromo-2', 4'-dichloroacetophenone, 6 parts of3-(4-chloro-o-tolyloxy)-1,2-propanediol, 3 parts of p-toluenesulfonicacid, 80 parts of n-butanol and 180 parts of benzene is stirred andrefluxed for 24 hours with water-separator. The solvent is removed invacuo and the residue is triturated in methanol. The produce is filteredoff and crystallized from petroleumether, yielding A + B2-(bromomethyl)-4-(4-chloro-2-tolyloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane.

EXAMPLE XVIII

A mixture of 13.6 parts of 2-bromo-1-(2,4-dichlorophenyl)-1-ethanone, 12parts of 3-(2,5-dimethylphenoxy)-1,2-propanediol, 3 parts of4-methylbenzenesulfonic acid, 80 parts of butanol and 180 parts ofbenzene is stirred and refluxed for 24 hours with water-separator. Thereaction mixture is evaporated and the residue is dissolved intrichloromethane. The solution is stirred with silicagel for 30 minutes.The latter is filtered off and the filtrate is evaporated, yielding A +B2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(2,5-dimethylphenoxymethyl)-1,3-dioxolaneas a residue.

EXAMPLE XIX

Following the procedure of Example XVIII and using equivalent amounts ofthe appropriate starting materials, the following dioxolanes areprepared:

    ______________________________________                                         ##STR34##                                                                    Isomer     R.sub.6       R.sub.7                                              ______________________________________                                        A + B      2,4-(Cl).sub.2                                                                              2,4,6-(Cl).sub.3                                     A + B      2,4-(Cl).sub.2                                                                              2-Cl,4-C(CH.sub.3).sub.3                             A + B      2,4-(Cl).sub.2                                                                              2,4,5-(Cl).sub.3                                     A + B      2,4-(Cl).sub.2                                                                              2,5-(Br).sub.2,4-CH.sub.3                            A + B      2,4-(Cl).sub.2                                                                              2-OC.sub.2 H.sub.5                                   A + B      2-Cl          4-Br                                                 ______________________________________                                    

EXAMPLE XX

A mixture of 13.6 parts of 2-bromo-2',4'-dichloroacetophenone, 18 partsof 3-(6-bromo-2-napthyloxy)-1,2-propanediol, 3 parts ofp-toluenesulfonic acid, 80 parts of n-butanol and 180 parts of benzeneis stirred and refluxed for 24 hours with water-separator. The reactionmixture is evaporated. The residue is dissolved in chloroform and thesolution is stirred with silica gel for one hour. The latter is filteredoff and the filtrate is evaporated. The residue is crystallized twice:first from diisopropylether and then from dibutylether, yielding A2-(bromomethyl)-4-(6-bromo-2-naphthyloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane.

EXAMPLE XXI

A mixture of 13.6 parts of 2-bromo-1-(2,4-dichlorophenyl)-1-ethanone,13.1 parts of 3-(2-naphtalenyloxy)-1,2-propanediol, 3 parts of4-methylbenzenesulfonic acid, 180 parts of benzene and 80 parts ofbutanol is stirred and refluxed for 12 hours with water-separator. Thereaction mixture is evaporated and the residue is triturated inmethanol. The product is filtered off and crystallized from 2-propanol,yielding A2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-[(2-naphthalenyloxy)methyl]-1,3-dioxo-lane;mp. 117.6° C.

EXAMPLE XXII

Following the procedure of Example XXI and using equivalent amounts ofthe appropriate starting materials, the following dioxolanes areprepared:

    ______________________________________                                         ##STR35##                                                                    Isomer R.sub.6     R.sub.7      Melting Point                                 ______________________________________                                        A      2,4-(Cl).sub.2                                                                            2-F          125.7°                                 A + B  4-CH.sub.3  4-Br         121.1°                                 A + B  4-Cl        4-Br         157.4°                                 A + B  4-Br        4-Br         158.7°                                 A      2,4-(Cl).sub.2                                                                            3-Br         112.7°                                 A      2,4-(Cl).sub.2                                                                            3,5-(CH.sub.3).sub.2                                                                       118.7°                                 A + B  2,4-(Cl).sub.2                                                                            4-CH.sub.2C.sub.6 H.sub.5                                                                  106.1°                                 A + B  4-OCH.sub.3 4-Br         117°                                   A       --         4-Br          85.6°                                 ______________________________________                                    

EXAMPLE XXIII

A mixture of 13.6 parts of 2-bromo-1-(2,4-dichlorophenyl)-1-ethanone,15.2 parts of 3-(4-chloro-1-naphthalenyloxy)-1,2-propanediol, 3 parts of4-methylbenzenesulfonic acid, 80 parts of butanol and 180 parts ofbenzene is stirred and refluxed for 24 hours with water-separator. Thereaction mixture is evaporated and the residue is triturated in2-propanol. The product is filtered off and crystallized from butanol,yielding A + B2-(bromomethyl)-4-(4-chloro-1-naphthalenyloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane;mp. 122.7° C.

EXAMPLE XXIV

A mixture of 13.6 parts of 2-bromo-1-(2,4-dichlorophenyl)-1-ethanone,15.8 parts of 3-(4-bromophenylthio)-1,2-propanediol, 3 parts of4-methylbenzenesulfonic acid, 180 parts of butanol and 90 parts ofbenzene is stirred and refluxed for 12 hours with water-separator. Thereaction mixture is evaporated and the residue is dissolved intrichloromethane. The solution is stirred with silica gel for 30minutes. The latter is filtered off and the filtrate is evaporated,yielding A + B2-(bromomethyl)-4-(4-bromophenylthiomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolaneas a residue.

EXAMPLE XXV

A mixture of 13.6 parts of 2-bromo-1-(2,4-dichlorophenyl)-1-ethanone,11.1 parts of 3-(phenylthio)-1,2-propanediol, 3 parts of4-methylbenzenesulfonic acid, 80 parts of butanol and 180 parts ofbenzene is stirred and refluxed for 24 hours with water-separator. Thereaction mixture is evaporated and the residue is dissolved intrichloromethane. The solution is stirred with silica gel for 30minutes. The latter is filtered off and the filtrate is evaporated,yielding A + B2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(phenylthiomethyl)-1,3-dioxolaneas a residue.

EXAMPLE XXVI

A mixture of 222.5 parts of 2-bromo-1-(2,4-dichlorophenyl)-1-ethanone,250 parts of 3-(4-bromophenoxy)-1,2-propanediol, 50 parts of4-methylbenzenesulfonic acid and 3150 parts of benzene is stirred andrefluxed in a four-necked, round-bottomed flask, equipped with awater-trap. After 16 hours the theoretical amount of water is evolved.The reaction mixture is allowed to cool to room temperature and washedsuccessively with diluted sodium hydroxide solution and twice withwater. The solvent is dried and removed in vacuo. The residue istriturated in methanol. The product is filtered off (the filtrate is setaside) and crystallized from butanol, yieldingA-2-(bromomethyl)-4-(p-bromophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane.

The filtrate (see above) is evaporated. The residue is dissolved in 210parts of 2,2'-oxybispropane and the solution is allowed to crystallize.The precipitated product is filtered off and discarded. The filtrate isevaporated and the residue is dissolved in 400 parts of a mixture ofhexane and trichloromethane (3:1 by volume). The undissolved part isfiltered off and discarded. The filtrate is purified twice bycolumn-chromatography over silica gel using a mixture of hexane andtrichloromethane (3:1 by volume) as eluent. The pure fractions arecollected and the eluent is evaporated. The residue solidifies ontriturating in petroleumether. The product is filtered off and dried,yieldingB-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane.

EXAMPLE XXVII

A mixture of 11.8 parts of 3-(2,6-dimethylphenoxy)-1,2-propanediol, 13.6parts of 2-bromo-1-(2,4-dichlorophenyl)-1-ethanone, 3 parts of4-methylbenzenesulfonic acid, 80 parts of butanol and 180 parts ofmethylbenzene is stirred and refluxed for 3 days. The reaction mixtureis evaporated and the residue is dissolved in 2,2'-oxybispropane. Thesolution is stirred for 30 minutes with silica gel. The latter isfiltered off and the filtrate is evaporated, yielding A + B2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(2,6-dimethylphenoxymethyl)-1,3-dioxolaneas a residue.

EXAMPLE XXVIII

A mixture of 11.2 parts of 2,2',4'-trichloroacetophenone, 14.9 parts of1-(2,4-dichlorophenoxy)-2,3-propanediol, 3 parts of p-toluenesulfonicacid and 240 parts of benzene is stirred and refluxed for 20 hours in afour-necked, round-bottomed flask, equipped with a water-trap. Thereaction mixture is washed successively with a diluted sodium hydroxidesolution and twice with water. The solvent is removed in vacuo. Theresidue is triturated in methanol for 3 hours. The precipitated productis filtered off and crystallized from 2-propanol, yieldingA-2-(chloromethyl)-4-(2,4-dichlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane;mp. 92.5° C.

EXAMPLE XXIX

A mixture of 24 parts of 3-(4-bromophenoxy)-1,2-propanediol, 28 parts of2-(bromomethyl)-2-(2,3,4-trichlorophenyl)-1,3-dioxolane, 4 parts of4-methylbenzenesulfonic acid, 40 parts of butanol and 225 parts ofmethylbenzene is stirred and refluxed for 2 days. The reaction mixtureis allowed to cool to room temperature and evaporated. The residue istriturated in methanol. The product is filtered off and crystallizedfrom 2-propanol, yieldingA-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(2,3,4-trichlorophenyl)-1,3-dioxolane.

EXAMPLE XXX

A mixture of 14.4 parts of 1-[2-(4-methylphenyl)ethyl]-ethanediol, 15.6parts of 2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane, 5-partsof 4-methylbenzenesulfonic acid, 225 parts of methylbenzene and 40 partsof butanol is stirred and refluxed for 3 days with water-separator. Thereaction mixture is evaporated and the residue is dissolved in2,2'-oxybispropane. The solution is stirred for 30 minutes with silicagel. The latter is filtered off and the filtrate is evaporated, yielding2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-[2-(4-methylphenyl)ethyl]-1,3-dioxolaneas a residue.

EXAMPLE XXXI

To a stirred and refluxing Grignard-complex, previously preparedstarting from 98 parts of 1-(chloromethyl)-2,4-dichlorobenzene and 14parts of magnesium in 70 parts of 1,1-oxybisethane, is added dropwise asolution of 46.5 parts of 2-(chloromethyl)oxirane in 350 parts of1,1'-oxybisethane. Upon completion, stirring at reflux temperature iscontinued overnight. The reaction mixture is cooled in an ice-bath anddecomposed by dropwise addition of 120 parts of a concentratedhydrochloric acid solution. The whole is poured onto water and thelayers are separated. The organic phase is washed three times withwater. The aqueous phase is extracted with 1,1'-oxybisethane. Thecombined organic phases are dried, filtered and evaporated. The residueis distilled, yielding 2,4-dichloro-α-(chloromethyl)benzenepropanol; bp.130° C. at 0.04 mm. pressure.

EXAMPLE XXXII

Following the procedure of Example XXXI and using equivalent amounts ofthe appropriate starting materials, the following compounds areprepared:

    ______________________________________                                         ##STR36##                                                                    R              boiling point                                                  ______________________________________                                        2-Cl         118° C. at 0.01 mm. pressure                              2,6-(Cl).sub.2                                                                             136° C. at 0.2 mm. pressure                               4-OCH.sub.3  140° C. at 0.2 mm. pressure                               4-Cl         130-135° C. at 0.3 mm. pressure                           ______________________________________                                    

EXAMPLE XXXIII

A solution of 87 parts of 2,4-dichloro-α-(chloromethyl)-benzenepropanolin 144 parts of concentrated sodium hydroxide solution and 350 parts of2,2'-oxybispropane is stirred overnight at room temperature. The productis extracted with 2,2'-oxybispropane. The extract is washed with water,dried, filtered and evaporated. The oily residue is distilled, yielding[2-(2,4-dichlorophenyl)ethyl]oxirane; bp. 90°-98° C. at 0.01 mm.pressure.

EXAMPLE XXXIV

Following the procedure of Example XXXIII and using equivalent amountsof the appropriate starting materials, the following oxirane derivativesare prepared:

    ______________________________________                                         ##STR37##                                                                    R              boiling point                                                  ______________________________________                                        2-Cl         66-70° C. at 0.01 mm. pressure                            2,6-(Cl).sub.2                                                                             85-89° C. at 0.01 mm. pressure                            4-OCH.sub.3  80-90° C. at 0.05 mm. pressure                            4-Cl         106-115° C. at 0.03 mm. pressure                          ______________________________________                                    

EXAMPLE XXXV

A mixture of 50 parts of [2-(2,4-dichlorophenyl)ethyl]-oxirane, 7 partsof ethanedioic acid, 300 parts of 1,4-dioxane and 150 parts of water isstirred and refluxed for 36 hours. The reaction mixture is evaporated.The residue is crystallized from 2,2'-oxybispropane. The product isfiltered off and dried at the air, yielding1-[2-(2,4-dichlorophenyl)ethyl]ethanediol; mp. 83.2° C.

EXAMPLE XXXVI

By repeating the procedure of Example XXXV and using therein anequivalent amount of the appropriate starting material, the followingcompounds are prepared:

1-[2-(2-chlorophenyl)ethyl]ethanediol; mp. 64.1° C.;

4-(2,6-dichlorophenyl)-1,2-butanediol; mp. 111.7° C.; and

1-[2-(4-chlorophenyl)ethyl]ethanediol; bp. 150° C. at 0.02 mm. pressure.

EXAMPLE XXXVII

To a stirred solution of 12 parts of2-[2-(4-methoxyphenyl)-ethyl]oxirane in 1.8 parts of sulfuric acid and160 parts of 2-propanone are added 100 parts of water. The whole isstirred for 2 days at room temperature. The reaction mixture is stirredwith a sodium bicarbonate solution and the product is extracted withtrichloromethane. The extract is dried, filtered and evaporated,yielding 1-[2-(4-methoxyphenyl)ethyl]-1,2-ethanediol as a residue.

EXAMPLE XXXVIII

A mixture of 13.6 parts of 2-bromo-1-(2,4-dichlorophenyl)-1-ethanone,14.1 parts of 1-[2-(2,4-dichlorophenyl)ethyl]ethanediol, 3 parts of4-methylbenzenesulfonic acid, 80 parts of butanol and 180 parts ofbenzene is stirred and refluxed for 24 hours. The reaction mixture isevaporated and the residue is stirred for 2 hours with 160 parts ofmethanol. The precipitated product is filtered off, yielding2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-[2-(2,4-dichlorophenyl)ethyl]-1,3-dioxolane.

EXAMPLE XXXIX

Following the procedure of Example XXXVIII and using an equivalentamount of the appropriate starting material, the following dioxolanesare prepared:

2-(bromomethyl)-4-[2-(2-chlorophenyl)ethyl]-2-(2,4-dichlorophenyl)-1,3-dioxolane;

2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-[2-(2,6-dichlorophenyl)ethyl]-1,3-dioxolane;and

A + b2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-[2-(4-methoxyphenyl)-ethyl]-1,3-dioxolane.

EXAMPLE XL

A mixture of 11.2 parts of 1-[2-(4-chlorophenyl)ethyl]-ethanediol, 15.6parts of 2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane, 4 partsof 4-methylbenzenesulfonic acid, 40 parts of butanol and 225 parts ofmethylbenzene is stirred and refluxed for 5 days with water-separator.The reaction mixture is evaporated and the residue is dissolved in2,2'-oxybispropane. The solution is stirred with silica gel. The latteris filtered off and the filtrate is evaporated, yielding2-(bromomethyl)-4-[2-(4-chlorophenyl)ethyl]-2-(2,4-dichlorophenyl)-1,3-dioxolaneas a residue.

EXAMPLE XLI

Following the procedure of Example XL and using therein an equivalentamount of 4-phenyl-1,2-butanediol as a starting material, there isobtained:2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(2-phenylethyl)-1,3-dioxolaneas a residue.

EXAMPLE XLII

To a stirred and refluxing Grignard-complex, previously preparedstarting from 89 parts of 4-(chloromethyl)-1,1'-biphenyl and 12.5 partsof magnesium in 350 parts of 1,1'-oxybisethane, is added dropwise asolution of 60 parts of 3-bromo-1-propene in 180 parts oftetrahydrofuran. Upon completion, stirring is continued for 2.50 hoursat reflux temperature. The reaction mixture is cooled and poured ontowater. The layers are separated and the aqueous phase is extracted with1,1'-oxybisethane. The combined organic phases are washed with water,dried, filtered and evaporated. The residue is filtered and the filtrateis evaporated, yielding 60 parts of 4-(3-butenyl)-1,1'-biphenyl as aresidue.

To a stirred mixture of 88 parts of 3-chlorobenzeneperoxoic acid and 650parts of dichloromethane are added dropwise 60 parts of4-(3-butenyl)-1,1'-biphenyl. Upon completion, stirring is continued overweek-end at room temperature. Then there are added dropwise 50 parts ofa potassium carbonate solution. The organic phase is separated, washedwith a sodium bisulfite solution and with water, dried, filtered andevaporated, yielding 63.5 parts (70.87%) of[2-([1,1'-biphenyl]-4-yl)ethyl]oxirane as an oily residue.

EXAMPLE XLIII

To a stirred mixture of 86 parts of 3-chlorobenzeneperoxoic acid and 650parts of dichloromethane are added dropwise (slowly) 53 parts of1-fluoro-4-(2-propenyl)benzene. Upon completion, stirring is continuedovernight at room temperature. Then there are added dropwise 92 parts ofa potassium carbonate solution and the layers are separated. The organicphase is washed with a sodium bisulfite solution, dried, filtered andevaporated, yielding 58.4 parts (98%) of 2-(4-fluorophenylmethyl)oxiraneas an oily residue.

EXAMPLE XLIV

To a stirred mixture of 44.5 parts of 4-chloro-1-naphthalenol and 115parts of 2-(chloromethyl)oxirane are added portionwise 17.1 parts ofpotassium hydroxide (exothermic reaction). When the exothermic reactionis ceased, the whole is heated to reflux and stirred at refluxtemperature for 2 hours. Water is added and the whole is extracted twicewith trichloromethane. The combined extracts are washed three times withwater, dried and evaporated. The residue is distilled, yielding 45.3parts of 2-[(4-chloro-1-naphthalenyloxy)-methyl]oxirane; bp. 150°-151°C. at 0.2 mm. pressure.

EXAMPLE XLV

To a stirred solution of 139 parts of 2-nitrophenol and 138 parts ofpotassium carbonate in 640 parts of 2-propanone are added dropwise 215parts of 2-(chloromethyl)oxirane. Upon completion, stirring is continuedfor 2 days at reflux. The formed precipitate is filtered off and thefilter-cake is washed with 2-propanone. The filtrate is evaporated. Theresidue is crystallized from a mixture of 2,2'-oxybispropane andpetroleumether (1:1 by volume). The product is filtered off and dried,yielding 38 parts (20%) of 2-(2-nitrophenoxymethyl)oxirane; mp. 56° C.

EXAMPLE XLVI

Following the procedure of Example XLV and using an equivalent amount ofa appropriately substituted phenol or naphthalenol in place of the2-nitrophenol used therein, the following 2-aryloxymethyloxiranes areobtained:

2-[(2-chloro-5-methylphenoxy)methyl]oxirane; bp. 115° C. at 0.05 mm.pressure;

2-(3,4,5-trichlorophenoxymethyl)oxirane as an oily residue;

2-(3-chloro-[1,1'-biphenyl]-4-yloxymethyl)oxirane as a residue; and

2-[(1,6-dibromo-2-naphthalenyloxy)methyl]oxirane as a solid residue.

EXAMPLE XLVII

To a stirred solution of 38 parts of 2-(2-nitrophenoxymethyl)-oxirane in10 parts of ethanedioic acid and 300 parts of 1,4-dioxane are added 100parts of water. The whole is stirred and refluxed for 2 days. Thereaction mixture is evaporated and the residue is crystallized from amixture of 2,2'-oxybispropane and petroleumether. The product isfiltered off and recrystallized from 2,2'-oxybispropane, yielding 29.5parts (13%) of 3-(2-nitrophenoxy)-1,2-propanediol; mp. 96° C.

EXAMPLE XLVIII

Following the procedure of Example XLVII and using an equivalent amountof an appropriately substituted oxirane in place of the2-[(2-nitrophenoxy)methyl]oxirane used therein, the following diols areobtained:

3-(4-chloro-1-naphthalenyloxy)-1,2-propanediol; mp. 120° C.;

3-(2-chloro-5-methylphenoxy)-1,2-propanediol; mp. 59° C.;

3-[4-(phenylmethyl)phenoxy]-1,2-propanediol; mp. 70° C.;

3-(3,4,5-trichlorophenoxy)-1,2-propanediol; mp. 64° C.;

3-(3-chloro-[1,1'-biphenyl]-4-yloxy)-1,2-propanediol; mp. 60° C.;

3-(1,6-dibromo-2-naphthalenyloxy)-1,2-propanediol; mp. 139° C.;

3-(4-bromophenyl)-1,2-propanediol; mp. 60.6° C.;

3-(4-fluorophenyl)-1,2-propanediol; bp. 125° C. at 0.05 mm. pressure;and

4-([1,1'-biphenyl]-4-yl)-1,2-butanediol; mp. 125.9° C.

EXAMPLE IL

A mixture of 13.5 parts of 1,2-butanediol, 37.5 parts2-bromo-1-(2,4-dichlorophenyl)ethanone, 2 parts of4-methylbenzenesulfonic acid, 40 parts of butanol and 225 parts ofmethylbenzene is stirred and refluxed for 24 hours with water-separator.The reaction mixture is cooled, washed twice with a sodium bicarbonatesolution, dried, filtered and evaporated. The residue is distilled,yielding 38 parts (80%) ofA+B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-ethyl-1,3-dioxolane; bp.125°-130° C. at 0.1 mm. pressure.

EXAMPLE L

Following the procedure of Example IL and using equivalent amounts ofthe appropriate starting materials, the following dioxolanes areprepared:

    ______________________________________                                         ##STR38##                                                                    R      R.sup.6      boiling point                                             ______________________________________                                        C.sub.2 H.sub.5                                                                      2-Cl        97-99° C. at 0.05 mm. pressure                      C.sub.2 H.sub.5                                                                      2-CH.sub.3  86-88° C. at 0.05 mm. pressure                      C.sub.2 H.sub.5                                                                      4-CH.sub.3  100° C. at 0.05 mm. pressure                        C.sub.2 H.sub.5                                                                      2-Br        114-115° C. at 0.05 mm. pressure                    C.sub.2 H.sub.5                                                                      3-Cl        140° C. at 0.6 mm. pressure                         C.sub.2 H.sub.5                                                                      2-Cl,4-Br   --                                                         C.sub.2 H.sub.5                                                                      4-OCH.sub.3 122° C. at 0.15 mm. pressure                        C.sub.2 H.sub.5                                                                      3,4,5-(Cl).sub.3                                                                          135° C. at 0.05 mm. pressure                        nC.sub.3 H.sub.7                                                                     2,4-(Cl).sub.2                                                                            102-125° C. at 0.05 mm. pressure                    nC.sub.4 H.sub.9                                                                     2,4-(Cl).sub.2                                                                            137-139° C. at 0.05 mm. pressure                    nC.sub.5 H.sub.11                                                                    2,4-(Cl).sub.2                                                                            140-145° C. at 0.03 mm. pressure                    nC.sub.6 H.sub.13                                                                    2,4-(Cl).sub.2                                                                            163-170° C. at 0.1 mm. pressure                     nC.sub.7 H.sub.15                                                                    2,4-(Cl).sub.2                                                                            160-165° C. at 0.05 mm. pressure                    nC.sub.8 H.sub.17                                                                    2,4-(Cl).sub.2                                                                            180-190° C. at 0.05 mm. pressure                    ______________________________________                                    

EXAMPLE LI

A mixture of 28.5 parts of 3-(3,4,5-trichlorophenoxy)-1,2-propanediol,18.4 parts of 2-bromo-1-(2,4-dichlorophenyl)ethanone, 3 parts of4-methylbenzenesulfonic acid, 40 parts of butanol and 225 parts ofmethylbenzene is stirred and refluxed over week-end. The reactionmixture is evaporated. The oily residue is purified bycolumn-chromatography over silica gel using trichloromethane as eluent.The pure fractions are collected and the eluent is evaporated, yielding17.5 parts (48%) ofA+B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(3,4,5-trichlorophenoxymethyl)-1,3-dioxolaneas a residue.

EXAMPLE LII

Following the procedure of Example LI and using equivalent amounts ofthe appropriate starting materials, the following dioxolanes areprepared:

A-2-(bromomethyl)-4-(2-bromo-4-methylphenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane;

2-(bromomethyl)-4-(2-chloro-5-methylphenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolaneas an oily residue;

A+b-2-(bromomethyl)-4-[(1,6-dibromo-2-naphthalenyloxy)methyl]-2-(2,4-dichlorophenyl)-1,3-dioxolane;and

A+b-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-methanol; bp.145°-150° C. at 0.05 mm. pressure.

EXAMPLE LIII

Following the procedure of Example LI and using equivalent amounts ofthe appropriate starting materials and dimethylbenzene as a solvent inplace of the methylbenzene used therein, the following dioxolanes arestill prepared:

A+b-4-([1,1'-biphenyl]-4-yloxymethyl)-2-(4-bromo-2-chlorophenyl)-2-(bromomethyl)-1,3-dioxolane;

A+b-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(phenylmethyl)-1,3-dioxolaneas a residue;

4-([1,1'-biphenyl]-2-yloxymethyl)-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolaneas an oily residue;

A+b-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-[(4-fluorophenyl)-thiomethyl]-1,3-dioxolaneas a residue;

A+b-2-(bromomethyl)-4-(4-chlorophenylmethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane;

A+b-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(4-methoxyphenylmethyl)-1,3-dioxolaneas a residue; and

A+b-4-([1,1'-biphenyl]-4-yloxymethyl)-2-(bromomethyl)-2-(3,4,5-trichlorophenyl)-1,3-dioxolaneas a residue.

EXAMPLE LIV

A mixture of 15.2 parts of 2-bromo-1-(2,4-dichlorophenyl)-ethanone, 17.6parts of 2-(2,3-dihydroxypropoxy)benzonitrile, 3 parts of4-methylbenzenesulfonic acid, 40 parts of 1-butanol and 225 parts ofdimethylbenzene is stirred and refluxed for 3 days with water-separator.The reaction mixture is evaporated. The residue is triturated inmethanol. The product is filtered off and dried, yielding 10 parts (45%)ofA-2-[2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-ylmethoxy]benzonitrile.

EXAMPLE LV

A mixture of 13.6 parts of butyl 4-(2,3-dihydroxypropoxy)-benzoate, 15.2parts of 2-bromo-1-(2,4-dichlorophenyl)ethanone, 3 parts of4-methylbenzenesulfonic acid, 40 parts of 1-butanol and 225 parts ofdimethylbenzene is stirred and refluxed for 3 days with water-separator.The reaction mixture is evaporated and the residue is triturated inmethanol. The product is filtered off and crystallized from 2-propanol,yielding 8.7 parts (39%) of A-butyl4-[2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-ylmethoxy]benzoate.

EXAMPLE LVI

A mixture of 15.2 parts of 2-bromo-1-(2,4-dichlorophenyl)ethanone, 16.7parts of 3-(3-chloro-[1,1'-biphenyl]-4-yloxy)-1,2-propanediol, 3 partsof 4-methylbenzenesulfonic acid, 40 parts of butanol and 225 parts ofdimethylbenzene is stirred and refluxed for 2 days with water-separator.The reaction mixture is allowed to cool to room temperature and2,2'-oxybispropane is added. The organic phase is washed with a dilutedsodium hydroxide solution 5N and with water, dried, filtered andevaporated. The residue is triturated in a mixture of 2,2'-oxybispropaneand petroleumether. The product is filtered off (the filtrate is setaside) and dried, yielding 12.5 parts ofA-2-(bromomethyl)-4-(3-chloro-[1,1'-biphenyl]-4-yloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane.The filtrate (see above) is evaporated. The residue is dissolved intrichloromethane and the solution is stirred with silica gel. The latteris filtered off and the filtrate is evaporated, yielding 10 parts ofA+B-2-(bromomethyl)-4-(3-chloro-[1,1'-biphenyl]-4-yloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolaneas a residue.

EXAMPLE LVII

A mixture of 18.1 parts of 3-[4-(phenylmethyl)phenoxy]-1,2-propanediol,13.4 parts of 2-bromo-1-(2,4-dichlorophenyl)ethanone, 3 parts of4-methylbenzenesulfonic acid, 40 parts of butanol and 225 parts ofmethylbenzene is stirred and refluxed over week-end. The reactionmixture is evaporated and the oily residue is triturated in methanol.The product is filtered off (the filtrate is set aside), yielding 15parts ofA-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-[4-(phenylmethyl)phenoxymethyl]-1,3-dioxolane;mp. 96° C. The filtrate, which was set aside, is evaporated. The oilyresidue is purified by column-chromatography over silica gel using amixture of trichloromethane and 20% of hexane as eluent. The purefractions are collected and the eluent is evaporated, yielding 13 partsofB-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-[4-(phenylmethyl)phenoxymethyl]-1,3-dioxolaneas an oily residue.

EXAMPLE LVIII

A mixture of 14.9 parts of 3-(2-nitrophenoxy)-1,2-propanediol, 13.4parts of 2-bromo-1-(2,4-dichlorophenyl)ethanone, 3 parts of4-methylbenzenesulfonic acid, 40 parts of butanol and 225 parts ofmethylbenzene is stirred and refluxed over week-end. The reactionmixture is evaporated and the oily residue is dissolved intrichloromethane. The solution is washed with a diluted sodium hydroxidesolution 20% and with water, dried, filtered and evaporated. The oilyresidue is crystallized from 2,2'-oxybispropane while stirring. Theproduct is filtered off (the filtrate is set aside), yielding 8.5 partsofA-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(2-nitrophenoxymethyl)-1,3-dioxolane.The filtrate which was set aside, is evaporated. The oily residue ispurified twice by column-chromatography over silica gel using, firsttrichloromethane and second a mixture of trichloromethane and 20% ofhexane as eluent. The pure fractions are collected and the eluent isevaporated, yielding 14.5 parts ofB-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(2-nitrophenoxymethyl)-1,3-dioxolaneas an oily residue.

EXAMPLE LIX

To a stirred and hot (50° C.) solution of 64 parts of1-(3-bromo-4-methylphenyl)-1-ethanone in 160 parts of 1-butanol areadded dropwise, during a 1 hour-period, 48 parts of bromine withoutexternal heating. After stirring for 1 hour at room temperature, thereare added successively 21.7 parts of 1,2-ethanediol, 6 parts of4-methylbenzenesulfonic acid and 720 parts of benzene and the whole isstirred and refluxed overnight with water-separator. The reactionmixture is evaporated and the residue is taken up in 2,2'-oxybispropane.The resulting solution is washed successively once with a diluted sodiumhydroxide solution and three times with water, dried, filtered andevaporated. The residue is distilled, yielding 57 parts (57%) of2-(bromomethyl)-2-(3-bromo-4-methylphenyl)-1,3-dioxolane; bp. 126°-130°C. at 0.1 mm. pressure.

EXAMPLE LX

Following the procedure of Example LIX and using an equivalent amount ofan appropriate 1-aryl-1-ethanone in place of the1-(3-bromo-4-methylphenyl)-1-ethanone used therein the following2-aryl-2-(bromomethyl)-1,3-dioxolanes are prepared:

2-(bromomethyl)-2-(4-chloro-2-methylphenyl)-1,3-dioxolane;

2-(bromomethyl)-2-(3,5-dichlorophenyl)-1,3-dioxolane; mp. 58° C.;

2-(bromomethyl)-2-(2,3-dichlorophenyl)-1,3-dioxolane; bp. 135°-137° C.at 0.1 mm. pressure;

2-(bromomethyl)-2-(2,4,5-trichlorophenyl)-1,3-dioxolane; bp. 146°-147°C. at 0.3 mm. pressure; and

2-(bromomethyl)-2-(2-chloro-4-methoxyphenyl)-1,3-dioxolane; mp. 53° C.

EXAMPLE LXI

To a stirred solution of 112 parts of 4-(2-bromoacetyl)-benzonitrile in320 parts of butanol are added 5 parts of 4-methylbenzenesulfonic acidand 360 parts of benzene. Then there are added dropwise 46.5 parts of1,2-ethanediol. Upon completion, stirring is continued for 4 hours atreflux. The reaction mixture is evaporated. The oily residue iscrystallized from 2,2'-oxybispropane. The product is filtered off andrecrystallized from methanol, yielding 95.12 parts of4-[2-(bromomethyl)-1,3-dioxolan-2-yl]benzonitrile; mp. 92.4° C.

EXAMPLE LXII

Following the procedure of Example LXI and using an equivalent amount ofan appropriate 1-aryl-2-bromo-1-ethanone in place of the4-(2-bromoacetyl)benzonitrile used therein, the following2-aryl-2-(bromomethyl)-1,3-dioxolanes are prepared:

2-(bromomethyl)-2-(2-naphthalenyl)-1,3-dioxolane; mp. 64° C.;

2-(bromomethyl)-2-(4-bromo-2-methylphenyl)-1,3-dioxolane; mp. 86° C.;

2-(bromomethyl)-2-(3-bromophenyl)-1,3-dioxolane; mp. 50° C.; and

2-(bromomethyl)-2-(3-nitrophenyl)-1,3-dioxolane; mp. 88° C.

EXAMPLE LXIII

A mixture of 19.8 parts of 3-(4-bromophenoxy)-1,2-propanediol, 15.6parts of 2-(bromomethyl)-2-(3,5-dichlorophenyl-1,3-dioxolane, 4 parts of4-methylbenzenesulfonic acid, 40 parts of butanol and 225 parts ofbenzene is stirred and refluxed for 2 days with water-separator. Thereaction mixture is allowed to cool to room temperature and the solventis removed by evaporation in vacuo. The residue is triturated inmethanol. The product is filtered off and crystallized from 2-propanolyielding 5.5 parts (22%) ofA-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(3,5-dichlorophenyl)-1,3-dioxolane.

EXAMPLE LXIV

Following the procedure of Example LXIII and using equivalent amounts ofthe appropriate starting materials, the following dioxolanes areprepared by carrying out the reaction in the indicated solvent:

Using methylbenzene as a solvent there are prepared:

A-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(4-chloro-2-methylphenyl)-1,3-dioxolane;mp. 155° C.;

A-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(3-bromophenyl)-1,3-dioxolane;mp. 92.2° C.;

A-2-(bromomethyl)-2-(4-bromo-2-methylphenyl)-4-(4-bromophenoxymethyl)-1,3-dioxolane;

A-2-(bromomethyl)-2-(3-bromo-4-methylphenyl)-4-(4-bromophenoxymethyl)-1,3-dioxolane;mp. 100° C.;

A-4-[2-(bromomethyl)-4-(4-bromophenoxymethyl)-1,3-dioxolan-2-yl]-benzonitrile;

A-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(3-nitrophenyl)-1,3-dioxolane;and

A-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(2,3-dichlorophenyl)-1,3-dioxolane.

Using dimethylbenzene as a solvent there are prepared:

A+b-4-([1,1'-biphenyl]-4-yloxymethyl)-2-(bromomethyl)-2-(2-naphthalenyl)-1,3-dioxolane;mp. 160.8° C.;

A-4-([1,1'-biphenyl]-4-yloxymethyl)-2-(bromomethyl)-2-(2-chloro-4-methoxyphenyl)-1,3-dioxolane;

A+b-2-(bromomethyl)-4-ethyl-2-(2,3,4-trichlorophenyl)-1,3-dioxolane; bp.145° C. at 0.1 mm. pressure;

A+b-4-([1,1'-biphenyl]-4-yloxymethyl)-2-(bromomethyl)-2-(2,4,5-trichlorophenyl)-1,3-dioxolaneas a residue;

A+b-2-(bromomethyl)-2-(2,3-dichlorophenyl)-4-ethyl-1,3-dioxolane; bp.131°-133° C. at 0.1 mm. pressure;

A+b-2-(bromomethyl)-2-(2-chloro-4-methoxyphenyl)-4-ethyl-1,3-dioxolane;bp. 142°-144° C. at 0.3 mm. pressure;

A+b-2-(bromomethyl)-2-(4-chloro-2-methylphenyl)-4-ethyl-1,3-dioxolane;bp. 118° C. at 0.15 mm. pressure; and

A+b-2-(bromomethyl)-4-ethyl-2-(2-naphthalenyl)-1,3-dioxolane as aresidue.

EXAMPLE LXV

To a stirred and warm solution of 6.5 parts of 1,2-butanediol, 13 partsof 1-(4-chloro-2-methoxyphenyl)ethanone and 40 parts of butanol areadded dropwise (slowly) 5.7 parts of bromine at about 40° C. Afterstirring for 30 minutes, there are added 2 parts of4-methylbenzenesulfonic acid and 225 parts of methylbenzene and thewhole is stirred and refluxed overnight with water-separator. Thereaction mixture is cooled, washed with a potassium carbonate solution,dried filtered and evaporated. The residue is distilled, yielding 17parts (63%) ofA+B-2-(bromomethyl)-2-(4-chloro-2-methoxyphenyl)-4-ethyl-1,3-dioxolane;bp. 135°-140° C. at 0.3 mm. pressure.

EXAMPLE LXVI

Following the procedure of Example LXV and using an equivalent amount of1-(2,4,5-trichlorophenyl)ethanone in place of the1-(4-chloro-2-methoxyphenyl)ethanone, there is obtained:

A+b-2-(bromomethyl)-4-ethyl-2-(2,4,5-trichlorophenyl)-1,3-dioxolane; bp.145° C. at 0.2 mm. pressure.

EXAMPLE LXVII

To a stirred solution of 53 parts of 1-(2,4-dibromophenyl)ethanone in105 parts of 1,1'-oxybisethane, are added dropwise, during a 2hours-period, 32 parts of bromine. Then there are added carefully 68parts of 1H-imidazole and 135 parts of N,N-dimethylformamide and thewhole is stirred for 2 hours at 50° C. Upon the addition of water, theproduct precipitates. It is filtered off, washed with water anddissolved in trichloromethane. The solution is dried, filtered andevaporated. The residue is converted into the hydrochloride salt in2-propanone and 2-propanol. Upon the addition of 2,2'-oxybispropane, theproduct is crystallized. It is filtered off, washed with 2-propanone andrecrystallized from a mixture of ethanol and 2,2'-oxybispropane,yielding 28.3 parts of1-(2,4-dibromophenyl)-2-(1H-imidazol-1-yl)ethanone hydrochloride; mp.204.7° C.

EXAMPLE LXVIII

To a stirred solution of 78.7 parts of2-bromo-1-(2-chloro-4-fluorophenyl)ethanone in 140 parts of1,1'-oxybisethane are added carefully 106.4 parts of 1H-imidazole. Uponcompletion, there are added 180 parts of N,N-dimethylformamide and thewhole is stirred for 2 hours at 50° C. After the addition of water, theproduct is extracted twice with trichloromethane. The combined extractsare washed three times with water, dried, filtered and evaporated. Theresidue is converted into the hydrochloride salt in4-methyl-2-pentanone, 2,2'-oxybispropane and 2-propanol. The salt isfiltered off and crystallized from a mixture of ethanol and2,2'-oxybispropane, yielding 1.5 parts of1-(2-chloro-4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanone hydrochloride;mp. 197.4° C.

EXAMPLE LXIX

A. To a stirred mixture of 67.2 parts ofA+B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-methanol and100 parts of pyridine are added dropwise 27.2 parts of benzoyl chloridewhile cooling at a temperature below 10° C. Upon completion, stirring iscontinued for 2.50 hours at room temperature. The reaction mixture ispoured onto water and the product is extracted with trichloromethane.The extract is washed successively with a diluted hydrochloric acidsolution, to remove the last traces of pyridine, and with water, driedfiltered and evaporated. The oily residue is triturated in methanol. Thesolid product is filtered off (the filtrate is set aside) andcrystallized twice from ethanol, yielding 28 parts ofcis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-ylmethylbenzoate; mp. 118.3° C. The filtrate (see above) is evaporated. The oilyresidue is purified by column-chromatography over silica gel using2,2'-oxybispropane as eluent. The pure fractions are collected and theeluent is evaporated. The oily residue is triturated in methanol. Thesolid product is purified by column-chromatography over silica gel usingtrichloromethane and hexane (30:70) as eluent. The pure fractions arecollected and the eluent is evaporated, yielding 17.5 parts oftrans-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-ylmethylbenzoate; mp. 68.6° C.

B. A mixture of 12 parts ofcis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-ylmethylbenzoate, 7.5 parts of sodium hydroxide solution 60%, 100 parts of waterand 200 parts of 1,4-dioxane is stirred and refluxed for 1 hour. Thereaction mixture is cooled, poured onto water and the product isextracted with trichloromethane. The extract is washed with water,dried, filtered and evaporated. The oily residue is purified bycolumn-chromatography over silica gel using a mixture oftrichloromethane, hexane and methanol (50:49:1) as eluent. The purefractions are collected and the eluent is evaporated, yielding 4.5 partsof cis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-methanolas a residue.

Following the procedure of Example LXIX-B and using an equivalent amountof trans-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-ylmethylbenzoate in place of thecis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-ylmethylbenzoate, there is obtained:

trans-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-methanol asa residue.

EXAMPLE LXX

A mixture of 4.5 parts of methanesulfonyl chloride, 10 parts ofcis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanoland 50 parts of pyridine is allowed to stand for 3 hours at roomtemperature. The reaction mixture is poured onto water. The precipitatedproduct is filtered off and crystallized from benzene, yielding 10.3parts (87%) ofcis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethylmethanesulfonate; mp. 111.7° C.

EXAMPLE LXXI

A mixture of 32 parts of 1,2,4-butanetriol, 60 parts of2-bromo-1-(2,4-dichlorophenyl)ethanone, 2 parts of4-methylbenzenesulfonic acid, 40 parts of butanol and 225 parts ofmethylbenzene is stirred and refluxed overnight with water-separator.The reaction mixture is cooled, washed with a potassium carbonatesolution, dried, filtered and evaporated. The residue is purified bycolumn-chromatography over silica gel using a mixture oftrichloromethane and methanol (99:1) as eluent. The pure fractions arecollected and the eluent is evaporated, yielding 34 parts (43%) ofA+B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-ethanol as aresidue.

To a stirred mixture of 20 parts ofA+B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-ethanol and50 parts of pyridine are added dropwise, 6.9 parts of methanesulfonylchloride. Upon completion, stirring at room temperature is continued for2 hours. The reaction mixture is poured onto water and the product isextracted twice with 1,1'-oxybisethane. The combined extracts are washedsuccessively twice with a diluted hydrochloric acid solution and oncewith water, dried, filtered and evaporated, yielding 25 parts (100%) ofA+B-{2-[2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]ethyl}methanesulfonateas a residue.

To a stirred mixture of 25 parts ofA+B-{2-[2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]ethyl}methanesulfonateand 100 parts of dimethylsulfoxide are added 2.2 parts of sodium hydridedispersion 78% at room temperature. Stirring is continued for 3 hours at50° C. The reaction mixture is poured onto water and the product isextracted twice with 2,2'-oxybispropane. The combined extracts arewashed twice with water, dried, filtered and evaporated. The residue ispurified by column-chromatography over silica gel using trichloromethaneas eluent. The pure fractions are collected and the eluent isevaporated, yielding 15 parts (79%) ofA+B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-ethenyl-1,3-dioxolane as aresidue.

B. FINAL PRODUCTS OF FORMULA I EXAMPLE LXXII

A mixture of 1.1 parts of imidazole, 1 part of2-(bromomethyl)-2,4-bis(4-chlorophenyl)-1,3-dioxolane, 0.4 parts ofpotassium iodide and 20 parts of dimethylformamide is stirred andrefluxed for 12 hours. Water is added and the product is extracted with1,1'-oxybisethane. The extract is washed twice with water, dried,filtered and evaporated. The residue of1-[2,4-bis(4-chlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazole isconverted into the nitrate salt. The crude salt is filtered off andcrystallized from a mixture of 2-propanol and 2,2'-oxybispropane,yielding 1-[2,4-bis(4-chlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 192.3° C.

EXAMPLE LXXIII

A mixture of 7 parts of imidazole, 7.5 parts of2-(bromomethyl)-2-(4-chlorophenyl)-4-phenyl-1,3-dioxolane, 2 parts ofsodium iodide and 100 parts of N,N-dimethylformamide is stirred andrefluxed for 48 hours. The reaction mixture is allowed to cool to roomtemperature and is poured into water. The product is extracted twicewith benzene. The extract is washed twice with water and the solvent isremoved in vacuo. The residue of1-[2-(4-chlorophenyl)-4-phenyl-1,3-dioxolan-2-ylmethyl]-imidazole isconverted into the nitrate salt in 4-methyl-2-pentanone and2,2'-oxybispropane. The crude salt is filtered off and crystallized from4-methyl-2-pentanone, yielding1-[2-(4-chlorophenyl)-4-phenyl-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 153.2° C.

EXAMPLE LXXIV

Following the procedure of Example LXXIII and using equivalent amountsof the appropriate starting materials, the following imidazoles andimidazole acid addition salts are prepared:

    ______________________________________                                         ##STR39##                                                                                                    Melting point                                 R.sub.6  R.sub.7    Acid salt   of Salt                                       ______________________________________                                        4-Cl     2,4-(Cl).sub.2                                                                           HNO.sub.3   196.6°                                 4-Br     4-Cl       HNO.sub.3   152.6°                                 4-Br     2,4-(Cl).sub.2                                                                           HNO.sub.3   205.3°                                 2,4-Cl.sub.2                                                                            --        2(COOH).sub.2                                                                             107.7°                                 4-OCH.sub.3                                                                            4-Cl       HNO.sub.3   196.3°                                  --      2,4-(Cl).sub.2                                                                           HNO.sub.3   163.8°                                 2,4-(CL).sub.2                                                                         4-Cl       1.5(COOH).sub.2                                                                           119.9°                                  --      4-Cl       HNO.sub.3   134.7°                                 4-Cl     2-Cl       HNO.sub.3   183.8°                                 2-Cl     2,4-(Cl).sub.2                                                                           HNO.sub.3   164.2°                                 2,4-(Cl).sub.2                                                                         2-Cl       HNO.sub.3   151°                                   ______________________________________                                    

example lxxv

a mixture of 13.6 parts of imidazole, 18.5 parts of2-(bromomethyl)-2-(o-chlorophenyl)-4-(p-chlorophenyl)-1,3-dioxolane, 4parts of sodium iodide and 150 parts of dimethylformamide is stirred andrefluxed for 72 hours. Water is added and the product is extracted twicewith diisopropylether. The combined extracts are washed twice withwater, dried, filtered and evaporated. The residue is purified bycolumn-chromatography over silica gel using trichloromethane as eluent.The pure fractions are collected and the eluent is evaporated. Theresidue of1-[2-(o-chlorophenyl)-4-(p-chlorophenyl)-1,3-dioxolan-2-ylmethyl]-imidazoleis converted into the nitrate salt in 2-propanol and diisopropylether.The salt is filtered off and crystallized from a mixture of ethanol anddiisopropylether, yielding1-[2-(o-chlorophenyl)-4-(p-chlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 183.1° C.

EXAMPLE LXXVI

A mixture of 13.6 parts of imidazole, 18.6 parts of2-(bromomethyl)-4-(p-bromophenyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane,4 parts of sodium iodide and 150 parts of dimethylformamide is stirredand refluxed for 3 days. The reaction mixture is poured into water andthe product is extracted twice with diisopropylether. The combinedextracts are washed twice with water, dried, filtered, and evaporated.The residue is purified by column-chromatography over silica gel usingchloroform as eluent. The pure fractions are collected and the eluent isevaporated. The residue,1-[4-(p-bromophenyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazole,is converted into the nitrate salt in 2-propanol and diisopropylether.The salt is filtered off and crystallized from a mixture of 2-propanoland diisopropylether, yielding1-[4-(p-bromophenyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 141.9° C.

EXAMPLE LXXVII

A mixture of 13.6 parts of imidazole, 17.5 parts of2-(bromomethyl)-2-(p-bromophenyl)-4-(o-chlorophenyl)-1,3-dioxolane, 4parts of sodium iodide and 150 parts of dimethyl formamide is stirredand refluxed for 3 days. Water is added and the product is extractedtwice with diisopropylether. The combined extracts containing1-[2-(p-bromophenyl)-4-(o-chlorophenyl)-1,3-dioxolane-2-ylmethyl]imidazoleare washed twice with water and acidified with an excess of aconcentrated nitric acid solution. The nitrate salt is filtered off andcrystallized from a mixture of ethanol and diisopropylether, yielding1-[2-(p-bromophenyl)-4-(o-chlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 194.7° C.

EXAMPLE LXXVIII

Following the procedure of Example LXXVIII and using equivalent amountsof the appropriate starting materials, the following imidazoles andimidazole acid addition salts are prepared:

    ______________________________________                                         ##STR40##                                                                                                    Melting                                       R.sub.6  R.sub.7     Acid Salt  Point of Salt                                 ______________________________________                                        2,4-(Cl).sub.2                                                                         2,4-(Cl).sub.2                                                                            HNO.sub.3  161.2°                                 4-Br      --         HNO.sub.3  156.5°                                  --      4-Br        HNO.sub.3  131.1°                                 4-CH.sub.3                                                                             2,4-(Cl).sub.2                                                                            HNO.sub.3  193.6°                                 4-Br     4-Br        HNO.sub.3  144.3°                                 4-CH.sub.3                                                                             4-Cl        HNO.sub.3  200.8°                                 4-Cl     4-Br        HNO.sub.3  145.2°                                 4-CH.sub.3                                                                             4-Br        HNO.sub.3  210.5°                                 3-Cl     2,4-(Cl).sub.2                                                                            HNO.sub.3  165.4°                                 2-Cl     4-Br        HNO.sub.3  184.1°                                 4-CH.sub.3                                                                             2-Cl        HNO.sub.3  207.5°                                 4-Cl     4-CH.sub.3  HNO.sub.3  144.3°                                 4-Br     4-CH.sub.3  HNO.sub.3  140.2°                                 4-Cl     4-F         HNO.sub.3  163.2°                                 4-Br     4-F         HNO.sub.3  179.3°                                 ______________________________________                                    

example lxxix

to a stirred solution of 2.3 parts of sodium in 80 parts of methanol areadded 6.8 parts of imidazole, followed by the addition of 100 parts ofdimethyl formamide and the methanol is removed at atmospheric pressuretill an internal temperature of 130° C. is reached. Then there are added7 partsA-2-(bromomethyl)-2-(p-chlorophenyl)-4-(4-chloro-o-tolyloxymethyl)-1,3-dioxolaneand the mixture is stirred and refluxed for 3 hours. The reactionmixture is poured into water and the product is extracted with benzene.The extract is dried and evaporated in vacuo. The residue ofA-1-[2-(p-chlorophenyl)-4-(4-chloro-o-tolyloxymethyl)-1,3-dioxolan-2-ylmethyl]imidazoleis converted into the nitrate salt in 2-propanol. Upon the addition ofdiisopropylether, the salt is precipitated. It is filtered off andcrystallized from a mixture of methanol and diisopropylether, yieldingcis1-[2-(p-chlorophenyl)-4-(4-chloro-o-tolyloxymethyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 164.3° C.

EXAMPLE LXXX

Following the procedure of Example LXXIX and using equivalent amounts ofthe appropriate starting materials, the following imidazoles andimidazole acid addition salts are prepared:

    __________________________________________________________________________     ##STR41##                                                                    Isomer                                                                            R.sub.6                                                                            R.sub.7 Acid Salt                                                                            Melting Point of Salt                                 __________________________________________________________________________    trans                                                                             4-Cl 4-Cl,2-CH.sub.3                                                                       HNO.sub.3                                                                            190 - 190.7°                                   cis 4-Cl 4-CH.sub.3                                                                            HNO.sub.3                                                                            140.2°                                         trans                                                                             4-Cl 4-CH.sub.3                                                                            HNO.sub.3                                                                            160°                                           trans                                                                             4-Cl 4-Cl    HNO.sub.3                                                                            171.8 - 176.9°                                 cis 4-Cl 4-Cl    HNO.sub.3                                                                            165.8 - 169.6°                                 B   4-Cl 2,4-Cl  HNO.sub.3                                                                            160 - 165.3°                                   cis 4-Cl 4-F     HNO.sub.3                                                                            172.3 - 174.5°                                 trans                                                                             4-Cl 4-F     HNO.sub.3                                                                            175.9°                                         A   4-Cl 2-CH.sub.3                                                                            HNO.sub.3                                                                            134.6 - 145.4°                                 B   4-Cl 2-CH.sub.3                                                                            HNO.sub.3                                                                            156.6 - 161.6°                                 B   4-Cl 2-Cl    HNO.sub.3                                                                            170.5°                                         B   4-Cl 4-OCH.sub.3                                                                           HNO.sub.3                                                                            133.2°                                         __________________________________________________________________________

example lxxxi

to a stirred solution of 2.3 parts of sodium in 80 parts of methanol areadded 6.8 parts of imidazole, 150 parts of dimethylformamide and 2 partsof sodium iodide at room temperature. The methanol is removed atatmospheric pressue till an internal temperature of 130° C. is reached.Then there are added 8 parts ofA-2-(bromomethyl)-2-(p-chlorophenyl)-4-(2,4-dichlorophenoxymethyl)-1,3-dioxolaneand the whole is stirred and refluxed for 2 hours. The reaction mixtureis allowed to cool to room temperature and water is added (400 parts).The reaction mixture is diluted with 80 parts of diisopropylether,whereupon the product is crystallized. It is filtered off andrecrystallized from 4-methyl-2-pentanone, yieldingA-1-[2-(p-chlorophenyl)-4-(2,4-dichlorophenoxymethyl)-1,3-dioxolane-2-ylmethyl]imidazole;mp. 175.4°-179.5° C.

EXAMPLE LXXXII

Following the procedure of Example LXXXI but substituting for theA-2-(bromomethyl)-2-(p-chlorophenyl)-4-(2,4-dichlorophenoxymethyl)-1,3-dioxolaneused therein equivalent amounts ofA-2-(bromomethyl)-4-(o-chlorophenoxymethyl)-2-(p-chlorophenyl)-1,3-dioxolaneandA-2-(bromomethyl)-2-(p-chlorophenyl)-4-(p-methoxyphenoxymethyl)-1,3-dioxolanethere are preparedA-1-[4-(o-chlorophenoxymethyl)-2-(p-chlorophenyl)-1,3-dioxolan-2-ylmethyl[imidazole(mp. 140.8°-143.6°) andA-1-[2-p-chlorophenyl)-4-(p-methoxyphenoxymethyl)-1,3-dioxolan-2-ylmethyl]imidazole(mp. 111.1°).

EXAMPLE LXXXIII

To a stirred solution of 4.6 parts of sodium in 160 parts of methanolare added successively 13.6 parts of imidazole, 300 parts ofdimethylformamide and 4 parts of sodium iodide. The methanol isdistilled off at atmospheric pressure till an internal temperature of130° C. is reached. Then there are added 25.9 parts of A +B-2-(bromomethyl)-2-(p-chlorophenyl)-4-(2,6-dichlorophenoxymethyl)-1,3-dioxolaneand the whole is stirred at reflux temperature for 2 hours. The reactionmixture is allowed to cool to room temperature and poured onto water.The product is extracted twice with benzene. The combined extracts arewashed twice with water, dried and evaporated in vacuo. The residue,containing the "A" and "B"-isomers, is chromatographed over silica gelwith chloroform as eluent. The "A"-isomer is collected as an oily freebase and is converted into the nitrate salt in 2-propanol. The crudesalt is crystallized from 2-propanol, yielding 3.8 parts ofA-1-[2-(p-chlorophenyl)-4-(2,6-dichlorophenoxymethyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 145.8° C. The "B"-isomer is also collected as an oily freebase and is converted into the nitrate salt in 2-propanol anddiisopropylether. The crude salt is crystallized from 2-propanol,yielding 2.2 parts ofB-1-[2-(p-chlorophenyl)-4-(2,6-dichlorophenoxymethyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 197°-200.5° C.

EXAMPLE LXXXIV

To a stirred solution of 4.6 parts of sodium in 120 parts of methanolare added successively 13.6 parts of imidazole, 200 parts ofdimethylformamide and 2 parts of sodium iodide. The methanol is removedat atmospheric pressure, while stirring, till an internal temperature of130° C. is reached. Then there are added 21.5 parts of A +B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(o-tolyloxymethyl)-1,3-dioxolaneand the whole is stirred and refluxed for 2 hours. The reaction mixtureis allowed to cool to room temperature and poured onto water. Theproduct is extracted with benzene (twice). The extracts are washed twicewith water, dried, filtered and removed in vacuo. The residue ischromatographed over silica gel with chloroform as eluent. The"A"-isomer is collected and the eluent is evaporated. The free baseresidue is converted into the nitrate salt in 4-methyl-2-pentanone. Uponthe addition of diisopropylether, the nitrate salt is precipitated. Itis filtered off and crystallized from 4-methyl-2-pentanone, yieldingA-1-[2-(2,4-dichlorophenyl)-4-(o-tolyloxymethyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate.; mp. 156.2° C.

The "B"-isomer is collected too and the eluent is evaporated. The freebase residue is converted into the oxalate salt in 4-methyl-2-pentanoneand diisopropylether. The crude salt is filtered off and crystallizedfrom 4-methyl-2-pentanone, yieldingB-1-[2-(2,4-dichlorophenyl)-4-(o-tolyloxymethyl)-1,3-dioxolan-2-ylmethyl]imidazolesesquioxalate; mp. 138.5° C.

EXAMPLE LXXXV

A mixture of 6.8 parts of imidazole, 8.5 parts ofB-2-(bromomethyl)-4-(p-chlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane,2 parts of sodium iodide and 100 parts of dimethylformamide is stirredand refluxed for 36 hours. The reaction mixture is allowed to cool toroom temperature and poured into water. The product is extracted twicewith benzene. The combined organic layers are washed twice with water,dried and the solvent is removed in vacuo. The residue is purified bycolumn-chromatography over silica gel using chloroform as eluent. Thepure fractions are collected and the eluent is evaporated. The residueisB-1-[4-(p-chlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazoleis converted into the oxalate salt in 4-methyl-2-pentanone: upon theaddition of diisopropylether, the salt is precipitated. It is filteredoff and crystallized from 4-methyl-2-pentanone, yielding 3.1 parts oftrans-1-[4-p-chlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazolesesquioxalate; mp. 101° C.

EXAMPLE LXXXVI

A mixture of 6.8 parts of imidazole, 8.9 parts ofB-2-(bromomethyl)-4-(2,4-dichlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane,3 parts of sodium iodide and 100 parts of dimethyl formamide is stirredand refluxed for 48 hours. The reaction mixture is allowed to cool toroom temperature and poured into water. The product is extracted twicewith benzene. The combined extracts are washed twice with water and thesolvent is removed in vacuo. The residue is purified bycolumn-chromatography over silica gel, using chloroform as eluent. Thepure fractions are collected and the eluent is evaporated. The residueofB-1-[4-(2,4-dichlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazoleis converted into the oxalate salt in 4-methyl-2-pentanone: upon theaddition of diisopropylether, the salt is precipitated. It is filteredoff and crystallized twice from 4-methyl-2-pentanone, yieldingB-1-[4-(2,4-dichlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazolesesquioxalate; mp. 121.2° C.

EXAMPLE LXXXVII

A mixture of 6.8 parts of imidazole, 7.8 parts ofA-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(phenoxymethyl)-1,3-dioxolane,4 parts of sodium iodide and 150 parts of dimethylformamide is stirredand refluxed for 3 days. The reaction mixture is allowed to cool to roomtemperature, poured into water and the product is extracted twice withdiisopropylether. The combined extracts containingA-1-[2-(2,4-dichlorophenyl)-4-(phenoxymethyl)-1,3-dioxolan-2-ylmethyl]imidazoleare washed twice with water and acidified with an excess of aconcentrated nitric acid solution. The salt is filtered off andcrystallized from a mixture of ethanol and diisopropylether, yielding5.6 parts ofA-1-[2-(2,4-dichlorophenyl)-4-(phenoxymethyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 180.5° C.

EXAMPLE LXXXVIII

Following the procedure of Example LXXXVII and using equivalent amountsof the appropriate starting materials, the following imidazoles andimidazole acid addition salts are prepared:

    ______________________________________                                         ##STR42##                                                                                                        Melting Point                             Isomer                                                                              R.sub.6  R.sub.7     Acid Salt                                                                              Of Salt                                   ______________________________________                                        A     2,4-(Cl).sub.2                                                                         3,4-(Cl).sub.2                                                                            HNO.sub.3                                                                              152.1°                             A     2,4-(Cl).sub.2                                                                         3-Cl        HNO.sub.3                                                                              120.9°                             A + B 2,4-(Cl).sub.2                                                                         4-Cl,2-CH.sub.3                                                                           HNO.sub.3                                                                              121.9°                             A     2,4-(Cl).sub.2                                                                         2,4-(Br).sub.2                                                                            HNO.sub.3                                                                              164.9°                             cis   2,4-(Cl).sub.2                                                                         2-F         HNO.sub.3                                                                              135.6°                             A     H        4-Br        HNO.sub.3                                                                              167.6°                             B     2,4-(Cl).sub.2                                                                         4-Br        HNO.sub.3                                                                              31.1°                              ______________________________________                                    

example lxxxix

a mixture of 6.8 parts of imidazole, 5 parts ofA-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(p-fluorophenoxymethyl)-1,3-dioxolane,2 parts of sodium iodide and 50 parts of dimethylformamide is stirredand refluxed for 24 hours. The reaction mixture is allowed to cool toroom temperature and then poured into water. The product is extractedtwice with benzene. The combined organic phases are washed twice withwater, dried, filtered, and evaporated in vacuo. The residue isA-1-[2-(2,4-dichlorophenyl)-4-(p-fluorophenoxymethyl)-1,3-dioxolan-2-ylmethyl]imidazoleis converted into the nitrate salt in 2-propanol. The crude salt isfiltered off and crystallized from 2-propanol, yielding 3.2 parts ofcis-1-[2-(2,4-dichlorophenyl)-4-(p-fluorophenoxymethyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 151°-152° C.

EXAMPLE XC

Following the procedure of Example LXXXIX and using equivalent amountsof the appropriate starting materials, the following imidazoles andimidazole acid addition salts are prepared:

    ______________________________________                                         ##STR43##                                                                                                        Melting Point                             Isomer                                                                              R.sub.6  R.sub.7     Acid Salt                                                                              of Salt                                   ______________________________________                                        A     2,4-(Cl).sub.2                                                                         4-CH.sub.3  HNO.sub.3                                                                              141.8°                             B     2,4-(Cl).sub.2                                                                         4-CH.sub.3  (COOH).sub.2                                                                           145.1°                             cis   2,4-(Cl).sub.2                                                                         4-OCH.sub.3 (COOH).sub.2                                                                           184.7°                             cis   2,4-(Cl).sub.2                                                                         4-Cl        HNO.sub.3                                                                              152.7°                             A     2,4-(Cl).sub.2                                                                         2,4-(Cl).sub.2                                                                            HNO.sub.3                                                                              146.5°                             A     2,4-(Cl).sub.2                                                                         4-Br        HNO.sub.3                                                                              158.9°                             A     2,4-(Cl).sub.2                                                                         4-Cl,3,5-CH.sub.3                                                                         HNO.sub.3                                                                              185.7°                             A     2,4-(Cl).sub.2                                                                         4-CN        HNO.sub.3                                                                              208°                               A     2,4-(Cl).sub.2                                                                         2-OCH.sub.3 2(COOH).sub.2                                                                          110.6°                             ______________________________________                                    

example xci

a mixture of 13.6 parts of imidazole, 22.2 parts of A +B-2-(bromomethyl)-4-(o-chlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane,4 parts of potassium iodide, and 150 parts of dimethylformamide isstirred and refluxed for 3 days. The reaction mixture is allowed to coolto room temperature, poured into water and the product is extractedtwice with diisopropylether. The combined extracts are washed twice withwater, dried, filtered and evaporated. The residue is purified bycolumn-chromatography over silica gel using chloroform as eluent,yielding two fractions.

The first fraction is evaporated and the residue ofA-1-[4-(o-chlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazoleis dissolved in a mixture of 4-methyl-2-pentanone and diisopropylether.The solution is acidified with an excess of a concentrated nitric acidsolution. The nitrate salt is filtered off and crystallized from amixture of 4-methyl-2-pentanone and diisopropylether, yieldingA-1-[4-(o-chlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 136.2° C.

The second fraction is evaporated and the residue ofB-1-[4-(o-chlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazoleis dissolved in a mixture of 4-methyl-2-pentanone and diisopropylether.The solution is acidified with an excess of oxalic acid. The oxalatesalt is filtered off and crystallized from 4-methyl-2-pentanone,yielding 4 parts ofB-1-[4-(o-chlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazoledioxalate; mp. 103.5° C.

EXAMPLE XCII

Following the procedure of Example XCI and using equivalent amounts ofthe appropriate starting materials, the following imidazoles andimidazole acid addition salts are prepared. Where only one isomer islisted, no second fraction was obtained from chromatography.

    ______________________________________                                         ##STR44##                                                                                                        Melting Point                             Isomer                                                                              R.sub.6  R.sub.7     Acid Salt                                                                              of Salt                                   ______________________________________                                        A     2,4-(Cl).sub.2                                                                         2,6-(Cl).sub.2                                                                            HNO.sub.3                                                                              159°                               cis   2,4-(Cl).sub.2                                                                         2-Br        HNO.sub.3                                                                              142.2°                             trans 2,4-(Cl).sub.2                                                                         2-Br        2(COOCH).sub.2                                                                         151.3°                             A     2,4-(Cl).sub.2                                                                         2,5-(CH.sub.3).sub.2                                                                      HNO.sub.3                                                                              180.9°                             B     2,4-(Cl).sub.2                                                                         2,5-(CH.sub.3).sub.2                                                                      1.5(COOH).sub.2                                                                        142.7°                             A     2,4-(Cl).sub.2                                                                         2,4,6-(Cl).sub.3                                                                          HNO.sub.3                                                                              181.6°                             B     2,4-(Cl).sub.2                                                                         2,4,6-(Cl).sub.3                                                                          2(COOH).sub.2                                                                          143.9°                             A     2,4-(Cl).sub.2                                                                         2-Cl,4-C(CH.sub.3).sub.3                                                                  HNO.sub.3                                                                              141.2°                             B     2,4-(Cl).sub.2                                                                         2-Cl,4-C(CH.sub.3).sub.3                                                                  HNO.sub.3                                                                              141.1°                             A     2,4-(Cl).sub.2                                                                         2,4,5-(Cl).sub.3                                                                          HNO.sub.3                                                                              196.1°                             B     2,4-(Cl).sub.2                                                                         2,4,5-(Cl).sub.3                                                                          1.5(COOH).sub.2                                                                        173.6°                             cis   2,4-(Cl).sub.2                                                                         2,5-(Br).sub.2, 4-CH.sub.3                                                                HNO.sub.3                                                                              175.4°                             A     2,4-(Cl).sub.2                                                                         20C.sub.2 H.sub.5                                                                         HNO.sub.3                                                                              117.7°                             A + B 2-Cl     4-Br        HNO.sub.3                                                                              145.3°                             B     2-Cl     4-Br        HNO.sub.3                                                                              152.7°                             A     2-Br     4-Br        HNO.sub.3                                                                              149.9°                             B     2-Br     4-Br        HNO.sub.3                                                                              169.3°                             A     2,4-(Cl).sub.2                                                                         2-Cl,6-CH.sub.3                                                                           HNO.sub.3                                                                              154.2°                             ______________________________________                                    

example xciii

a mixture of 13.6 parts of imidazole, 12 parts of A2-(bromomethyl)-4-(6-bromo-2-naphthyloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane,4 parts of potassium iodide and 150 parts of dimethylformamide isstirred and refluxed for 3 days. The reaction mixture is allowed to coolto room temperature, poured into water and the product is extractedtwice with benzene. The combined extracts are washed twice with water,dried, filtered and evaporated. The residue ofA-1-[4-(6-bromo-2-naphthyloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazoleis converted into the nitrate salt in 4-methyl-2-pentanone anddiisopropylether. The salt is filtered off and crystallized from amixture of methanol and diisopropylether, yielding A1-[4-(6-bromo-2-naphthyloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]imidazolenitrate; mp. 195.5° C.

EXAMPLE XCIV

A mixture of 6.8 parts of 1H-imidazole, 6 parts of A2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-[(2-naphthalenyloxy)methyl]-1,3-dioxolane,4 parts of potassium iodide and 150 parts of N,N-dimethylformamide isstirred and refluxed for 3 days. The reaction mixture is poured intowater and the product is extracted twice with 1,1'-oxybisethane. Thecombined extracts containingA-1-[2-(2,4-dichlorophenyl)-4-(2-naphthalenyloxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazoleare washed twice with water and acidified with an excess of aconcentrated nitric acid solution. The nitrate salt is filtered off andcrystallized from a mixture of ethanol and 2,2'-oxybispropane, yieldingcis-1-[2-(2,4-dichlorophenyl)-4-(2-naphthalenyloxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 156.3° C.

EXAMPLE XCV

A mixture of 9.7 parts of 1H-imidazole, 12.5 parts of A + B2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(4-methylphenyl)-1,3-dioxolane,3 parts of potassium iodide and 135 parts of N,N-dimethylformamide isstirred and refluxed for 72 hours. The reaction mixture is poured intowater and the product is extracted twice with 1,1'-oxybisethane. Theextract containingA-1-[4-(4-bromophenoxymethyl)-2-(4-methylphenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazoleis washed twice with water, and an excess of a concentrated nitric acidsolution and 2,2'-oxybispropane are added. The formed salt is filteredoff and crystallized from a mixture of ethanol and 2,2'-oxybispropane,yielding 5.6 parts of A1-[4-(4-bromophenoxymethyl)-2-(4-methylphenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 175.5° C.

EXAMPLE XCVI

Following the procedure of Example XCV but substituting for theA+B-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(4-methylphenyl)-1,3-dioxolaneused therein equivalent amounts ofA+B-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(4-chlorophenyl)-1,3-dioxolaneandA+B-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(4-bromophenyl)-1,3-dioxolanethere are preparedA-1-[4-(4-bromophenoxymethyl)-2-(4-chlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazoleand its nitrate salt (mp. 158°) andA-1-[4-(4-bromophenoxymethyl)-2-(4-bromophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazoleand its nitrate salt (mp. 170.8°).

EXAMPLE XCVII

A mixture of 20.8 parts of 1H-imidazole, 21 parts of A + B2-(bromomethyl)-4-(4-chloro-1-naphthalenyloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane,4 parts of potassium iodide and 135 parts of N,N-dimethylformamide isstirred and refluxed for 3 days. The reaction mixture is poured intowater and the product is extracted twice with 2,2'-oxybispropane. Thecombined extracts containing A + B1-[4-(4-chloro-1-naphthalenyloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazoleare washed twice with water and an excess of a concentrated nitric acidsolution is added. The nitrate salt is filtered off and crystallizedfrom a mixture of ethanol and 2,2'-oxybispropane, yielding A + B1-[4-(4-chloro-1-naphthalenyloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 136.7° C.

EXAMPLE XCVIII

A mixture of 20.4 parts of 1H-imidazole, 27.2 parts of A + B2-(bromomethyl)-4-(4-bromophenylthiomethyl)-2(2,4-dichlorophenyl)-1,3-dioxolane,4 parts of potassium iodide and 180 parts of N,N-dimethylformamide isstirred and refluxed for 3 days. The reaction mixture is poured intowater and the product is extracted twice with 1,1'-oxybisethane. Thecombined extracts are washed twice with water, dried, filtered andevaporated. The residue is purified by column-chromatography over silicagel using trichloromethane as eluent. The pure fractions are collectedand the eluent is evaporated. The residue of A+B-1-[4-(4-bromophenylthiomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazoleis converted into the nitrate salt in 4-methyl-2-pentanone and2,2'-oxybispropane. The salt is filtered off and crystallized from amixture of ethanol and 2,2'-oxybispropane. The product is filtered offand dried, yielding A + B1-[4-(4-bromophenylthiomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 170.0° C.

EXAMPLE IC

A mixture of 20.4 parts of 1H-imidazole, 20.5 parts of A + B2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(phenylthiomethyl)-1,3-dioxolane,4 parts of potassium iodide and 135 parts of N,N-dimethylformamide isstirred and refluxed for 3 days. The reaction mixture is poured intowater and the product is extracted twice with 1,1'-oxybisethane. Thecombined extracts are washed twice with water, dried, filtered andevaporated. The residue is purified by column-chromatography over silicagel using trichloromethane as eluent. The pure fractions are collectedand the eluent is evaporated. The residue of A + B1-[2-(2,4-dichlorophenyl)-4-(phenylthiomethyl)-1,3-dioxolane-2-ylmethyl]-1H-imidazoleis converted into the nitrate salt in 4-methyl-2-pentanone and2,2'-oxybispropane. The salt is filtered off and crystallized from amixture of ethanol and 2,2'-oxybispropane. The product is filtered offand dried, yielding A + B1-[2-(2,4-dichlorophenyl)-4-(phenylthiomethyl)-1,3-dioxolane-2-ylmethyl]-1H-imidazolenitrate; mp. 122.3° C.

EXAMPLE C

A mixture of 7.9 parts of 1H-imidazole, 11.5 parts of A + B2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(4-phenylphenoxymethyl)-1,3-dioxolane,4 parts of potassium iodide and 135 parts of N,N-dimethylformamide isstirred and refluxed for 3 days. The reaction mixture is poured ontowater and the product is extracted twice with 1,1'-oxybisethane. Thecombined extracts are washed with water, dried, filtered and evaporated.The residue is purified by column-chromatography over silica gel, usingtrichloromethane as eluent.

The first fraction is collected and the eluent is evaporated. Theresidue is converted into the nitrate salt in 4-methyl-2-pentanone and2,2'-oxybispropane. The salt is filtered off and crystallized from amixture of ethanol and 2,2'-oxybispropane, yielding A + B1-[2-(2,4-dichlorophenyl)-4-(4-phenylphenoxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 187.9° C.

The second fraction is collected and the eluent is evaporated. Theresidue is crystallized from 4-methyl-2-pentanone, yieldingtrans-1-[2-(2,4-dichlorophenyl)-4-(4-phenylphenoxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp. 155.7° C.

EXAMPLE CI

To a stirred sodium methoxide solution, prepared starting from 2.3 partsof sodium in 48 parts of methanol, is added a mixture of 6.8 parts of1H-imidazole and 180 parts of N,N-dimethylformamide. The methanol isdistilled off at normal pressure till an internal temperature of 125° C.is reached. Then there are added 22.8 parts of A + B2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(2,6-dimethylphenoxymethyl)-1,3-dioxolaneand 3 parts of potassium iodide. The whole is stirred and refluxed for24 hours. The reaction mixture is poured onto water and the product isextracted three times with 1,1'-oxybisethane. The combined extracts arewashed twice with water, dried, filtered and evaporated. The residue ispurified by column-chromatography over silica gel using trichloromethaneas eluent.

The first fraction (A-isomer) is collected and the eluent is evaporated.The residue is converted into the nitrate salt in 4-methyl-2-pentanoneand 2,2'-oxybispropane. The salt is filtered off and crystallized from amixture of ethanol and 2,2'-oxybispropane, yieldingA-1-[2-(2,4-dichlorophenyl)-4-(2,6-dimethylphenoxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 155.6° C.

The second fraction (B-isomer) is collected and the eluent isevaporated. The residue is converted into the nitrate salt in4-methyl-2-pentanone and 2,2'-oxybispropane. The salt is filtered offand crystallized from a mixture of 2-propanol and 2,2'-oxybispropane,yielding A + B1-[2-(2,4-dichlorophenyl)-4-(2,6-dimethylphenoxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 134.5° C.

EXAMPLE CII

A mixture of 8.6 parts of 1H-imidazole, 11.3 parts ofA-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(3,5-dimethylphenoxymethyl)-1,3-dioxolane,4 parts of potassium iodide and 135 parts of N,N-dimethylacetamide isstirred and refluxed for 3 days. The reaction mixture is poured ontowater and the product is extracted twice with 2,2'-oxybispropane. Thecombined extracts are washed twice with water and an excess of aconcentrated nitric acid solution is added. The formed nitrate salt isfiltered off and crystallized from a mixture of 2-propanol and2,2'-oxybispropane. The product is filtered off again and recrystallizedfrom 4-methyl-2-pentanone, yieldingA-1-[2-(2,4-dichlorophenyl)-4-(3,5-dimethylphenoxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate hydrate; mp. 122.6° C.

EXAMPLE CIII

A mixture of 5.4 parts of 1H-imidazole, 7.5 parts of A +B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-[4-(1-methylethyl)-phenoxymethyl]-1,3-dioxolane,3 parts of potassium iodide and 135 parts of N,N-dimethylacetamide isstirred and refluxed for 3 days. The reaction mixture is allowed to coolto room temperature, poured onto water and the product is extractedtwice with 2,2'-oxybispropane. The combined extracts are washed twicewith water and an excess of a concentrated nitric acid solution isadded. The formed nitrate salt is filtered off and crystallized from amixture of 2-propanol and 2,2'-oxybispropane, yielding A +B-1-{2-(2,4-dichlorophenyl)-4-[4-(1-methylethyl)phenoxymethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolenitrate.

EXAMPLE CIV

Following the procedure of Example CIII and using equivalent amounts ofthe appropriate starting materials, the following imidazoles andimidazole acid addition salts were prepared:

A-1-{2-(2,4-dichlorophenyl)-4-[4-(1,1-dimethylethyl)phenoxymethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolenitrate; mp. 169.5° C.

A-1-[4-(3,5-dichlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate hydrate; mp. 136.7° C.; and

A-1-[4-(4-chloro-3-methylphenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 142.8° C.

EXAMPLE CV

A mixture of 6.8 parts of 1H-imidazole, 8 parts ofA-2-(bromomethyl)-4-(p-bromophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane,3 parts of sodium iodide and 90 parts of N,N-dimethylformamide isstirred and refluxed for 3 days. The reaction mixture is cooled andpoured onto 500 parts of water. The product is extracted twice with 180parts of methylbenzene. The combined extracts are washed twice with 200parts of water, dried, filtered and evaporated. The residue is taken upin a mixture of methanol and 2,2'-oxybispropane, treated with activatedcharcoal and evaporated. The residue is converted into the nitrate saltin 4-methyl-2-pentanone. The salt is sucked off and the free base isliberated in the conventional manner. It is extracted with methylbenzeneand the extract is dried, filtered and evaporated. The residue istriturated in 2,2'-oxybispropane. The product is filtered off and dried,yieldingcis-1-[4-(4-bromophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp. 121.8° C.

EXAMPLE CVI

Following the procedure of Example CV and using equivalent amounts ofthe appropriate starting materials, the following imidazoles andimidazole acid additions salts are prepared:

1-{4-[2-(2-chlorophenyl)ethyl]-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl}-1H-imidazolenitrate; mp. 98.8° C.;

1-{2-(2,4-dichlorophenyl)-4-[2-(2,4-dichlorophenyl)ethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolenitrate; mp. 158.1° C.; and

A + b1-{2-(2,4-dichlorophenyl)-4-[2-(2,6-dichlorophenyl)ethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolenitrate; mp. 140.1° C.

EXAMPLE CVII

A mixture of 14.4 parts of 1H-imidazole, 18.5 parts of A + B2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-[2-(4-methoxyphenyl)ethyl]-1,3-dioxolane,5 parts of potassium iodide and 135 parts of N,N-dimethylacetamide isstirred and refluxed for 2 days. The reaction mixture is allowed to coolto room temperature and poured onto water. The product is extractedtwice with 2,2'-oxybispropane. The combined extracts are washed withwater, dried, filtered and evaporated. The residue is converted into theethanedioate salt in 4-methyl-2-pentanone and 2,2'-oxybispropane. Thesalt is filtered off and crystallized from a mixture of2,2'-oxybispropane and ethanol, yielding A + B1-{2-(2,4-dichlorophenyl)-4-[2-(4-methoxyphenyl)ethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolesesquiethanedioate; mp. 130.7° C.

EXAMPLE CVIII

Following the procedure of Example CVII and using equivalent amounts ofthe appropriate starting materials, the following imidazoles andimidazole acid addition salts are prepared:

1-{4-[2-(4-chlorophenyl)ethyl]-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl}-1H-imidazolediethanedioate; mp. 131.9° C.;

1-[2-(2,4-dichlorophenyl)-4-(2-phenylethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolesesquiethanedioate; mp. 117.8° C.; and

A + b1-{2-(2,4-dichlorophenyl)-4-[2-(4-methylphenyl)ethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolesesquiethanedioate hydrate; mp. 123.8° C.

EXAMPLE CIX

A mixture of 10.6 parts of 1H-imidazole, 15.8 parts ofA-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(2,3,4-trichlorophenyl)-1,3-dioxolane,3 parts of potassium iodide and 135 parts of N,N-dimethylacetamide isstirred and refluxed for 2 days. The reaction mixture is allowed to coolto room temperature and poured onto water. The product is extractedtwice with 1,1'-oxybisethane. The combined extracts are washed twicewith water and acidified with an excess of a concentrated nitric acidsolution. Upon the addition of 2,2'-oxybispropane, the formed nitratesalt is precipitated. It is filtered off and crystallized from a mixtureof ethanol and 2,2'-oxybispropane, yieldingA-1-[4-(4-bromophenoxymethyl)-2-(2,3,4-trichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 174.4° C.

EXAMPLE CX

A mixture of 17 parts of 1H-imidazole, 33.5 parts of A +B-2-(bromomethyl)-4-(2,3-dichlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane,3 parts of potassium iodide and 135 parts of N,N-dimethylacetamide isstirred and refluxed for 2 days. The reaction mixture is allowed to coolto room temperature and poured onto water. The product is extractedtwice with 1,1'-oxybisethane. The combined extracts are washed twicewith water, dried, filtered and evaporated. The residue is purified bycolumn-chromatography over silica gel, using trichloromethane as eluent.

The first fraction (A-isomer) is collected and the eluent is evaporated.The residue is converted into the ethanedioate salt in4-methyl-2-pentanone and 2,2'-oxybispropane. The salt is filtered offand crystallized from 4-methyl-2-pentanone, yieldingA-1-[4-(2,3-dichlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolediethanedioate; mp. 151.1° C.

The second fraction (B-isomer) is collected and the eluent isevaporated. The residue is converted into the ethanedioate salt in4-methyl-2-pentanone and 2,2'-oxybispropane. The salt is filtered offand crystallized from 4-methyl-2-pentanone, yieldingB-1-[4-(2,3-dichlorophenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolesesquiethanedioate; mp. 156.3° C.

EXAMPLE CXI

A mixture of 6.8 parts of 1H-imidazole, 10.2 parts ofA-2-(bromomethyl)-4-(2-bromo-4-methylphenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane,3 parts of potassium iodide and 135 parts of N,N-dimethylacetamide isstirred and refluxed for 2 days. The reaction mixture is allowed to coolto room temperature and the product is extracted twice with1,1'-oxybisethane. The combined extracts are washed twice with water andacidified with a concentrated nitric acid solution. The formed nitratesalt is filtered off and crystallized from a mixture of ethanol and2,2'-oxybispropane, yielding 5.4 parts ofA-1-[4-(2-bromo-4-methylphenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 137.1° C.

EXAMPLE CXII

Following the procedure of Example CXI and using an equivalent amount ofan appropriate 2-bromomethyl-1,3-dioxolane as a starting material, thefollowing imidazole acid addition salts are obtained:

    ______________________________________                                         ##STR45##                                                                                                          Melting                                                                       Point                                   Isomer R.sup.6   R.sup.7     Acid Salt                                                                              of Salt                                 ______________________________________                                        A      2-CH.sub.3 -4-Cl                                                                        4-Br        HNO.sub.3                                                                              159.3° C.                        A=cis  2-CH.sub.3 -4-Br                                                                        4-Br        HNO.sub.3                                                                              164.3° C.                        A=cis  3-Br      4-Br        HNO.sub.3                                                                              158.7° C.                        A=cis  3-Br-4-CH.sub.3                                                                         4-Br        HNO.sub.3                                                                              201.1° C.                        A=cis  4-CN      4-Br        HNO.sub.3                                                                              190.1° C.                        A      2,4-(Cl).sub.2                                                                          4-(C.sub.6 H.sub.5 -CH.sub.2)                                                             HNO.sub.3 . H.sub.2 O                                                                  110.3° C.                        A=cis  3,5-(Cl).sub.2                                                                          4-Br        HNO.sub.3                                                                              167.1° C.                        A= cis 3-NO.sub.2                                                                              4-Br        HNO.sub.3                                                                              148.8° C.                        A=cis  2,4-(Cl).sub.2                                                                          2-NO.sub.2  2(COOH).sub.2                                                                          95.2° C.                         B=trans                                                                              2,4-(Cl).sub.2                                                                          2-NO.sub.2  (COOH).sub.2                                                                           157.2° C.                        B=trans                                                                              2,4-(Cl).sub.2                                                                          4-(C.sub.6 H.sub.5 -CH.sub.2)                                                             (COOH).sub.2                                                                           137° C.                          A+B    2,4-(Cl).sub.2                                                                          2-(C.sub.6 H.sub.5)                                                                       HNO.sub.3                                                                              109.3° C.                        ______________________________________                                    

example cxiii

following the procedure of Example CXI and using equivalent amounts ofthe appropriate starting materials and N,N-dimethylformamide as asolvent, there is prepared:

cis-1-[2-(2,4-dichlorophenyl)-4-(2-methoxyphenoxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazoleethanedioate hemihydrate; mp. 123.6° C.

EXAMPLE CXIV

A mixture of 13.6 parts of 1H-imidazole, 10 parts ofA-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(4-fluorophenoxymethyl)-1,3-dioxolane,4 parts of sodium iodide and 90 parts of N,N-dimethylformamide isstirred and refluxed for 24 hours. After cooling, the reaction mixtureis poured onto ice-water and the product is extracted twice withbenzene. The combined extracts are washed with water, dried, filteredand evaporated. The residue is converted into the nitrate salt in2-propanol. The salt is filtered off and the free base is liberated inthe conventional manner.The product is extracted twice withtrichloromethane. The extract is washed with water, dried, filtered andevaporated. The oily residue is crystallized from a mixture of benzeneand petroleumether, yielding 3.94 parts ofcis-1-[2-(2,4-dichlorophenyl)-4-(4-fluorophenoxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp. 106.7° C.

EXAMPLE CXV

A mixture of 42 parts of 1H-imidazole, 63 parts ofA+B-4-([1,1'-biphenyl]-4-yloxymethyl)-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane,20 parts of potassium iodide and 675 parts of N,N-dimethylformamide isstirred and refluxed for 3 days. The reaction mixture is poured ontowater and the product is extracted with 2,2'-oxybispropane. The extractis dried, filtered and evaporated. The residue is converted into thenitrate salt in 4-methyl-2-pentanone and 2,2'-oxybispropane. The productis separated as an oil. The supernatant phase is decanted and theresidual oil solidifies on triturating in 4-methyl-2-pentanone. Thenitrate salt is filtered off and crystallized from ethanol, yielding 5parts ofcis-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 186.5° C.

EXAMPLE CXVI

A mixture of 11.5 parts of 1H-imidazole, 17.5 parts ofA+B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(3,4,5-trichlorophenoxymethyl)-1,3-dioxolane,3 parts of potassium iodide and 180 parts of N,N-dimethylacetamide isstirred and refluxed over week-end. The reaction mixture is poured ontowater and the product is extracted four times with 1,1'-oxybisethane.The combined extracts are washed a few times with water, dried, filteredand evaporated. The only residue is purified by column-chromatographyover silica gel using trichloromethane as eluent. The first fraction(A-isomer) is collected and the eluent is evaporated. The oily residueis converted into the nitrate salt in 4-methyl-2-pentanone. The salt isfiltered off and crystallized from a mixture of 4-methyl-2-pentanone and2,2'-oxybispropane, yielding, after drying, 7.5 parts (40%) ofcis-1-[2-(2,4-dichlorophenyl)-4-(3,4,5-trichlorophenoxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate.hydrate; mp. 149.9° C. The second fraction (B-isomer) iscollected and the eluent is evaporated. The oily residue is convertedinto the nitrate salt in 4-methyl-2-pentanone. The salt is filtered offand crystallized from a mixture of 4-methyl-2-pentanone and2,2'-oxybispropane, yielding, after drying, 6.2 parts (27%) oftrans-1-[2-(2,4-dichlorophenyl)-4-(3,4,5-trichlorophenoxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 169.3° C.

EXAMPLE CXVII

Following the procedure of Example CXVI and using equivalent amounts ofthe appropriate starting materials, the following imidazoles andimidazole acid addition salts are prepared. When only one isomer islisted, no second fraction was obtained from chromatography.

cis-1-[4-(2-chloro-5-methylphenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp. 131.7° C.;

trans-1-[4-(2-chloro-5-methylphenoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolesesquiethanedioate; mp. 148.7° C.; and

A-1-{4-[(1,6-dibromo-2-naphthalenyloxy)methyl]-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl}-1H-imidazolenitrate; mp. 179.4° C.

EXAMPLE CXVIII

A mixture of 4.5 parts of 1H-imidazole, 6.5 parts ofA-2-(bromomethyl)-4-(4-bromophenoxymethyl)-2-(2,3-dichlorophenyl)-1,3-dioxolaneand 125 parts of N,N-dimethylacetamide is stirred and refluxed for 2days. The reaction mixture is allowed to cool to room temperature,poured onto water and the product is extracted twice with1,1'-oxybisethane. The combined extracts are washed twice with water andan excess of a concentrated nitric acid solution is added. The formednitrate salt is filtered off and crystallized from 4-methyl-2-pentanone,yielding 5 parts (68%) ofcis-1-[4-(4-bromophenoxymethyl)-2-(2,3-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 138.9° C.

EXAMPLE CXIX

Following the procedure of Example CXVIII and using equivalent amountsof the appropriate starting materials, the following imidazole acidaddition salts are prepared:

cis-1-[4-(3-chloro-[1,1'-biphenyl]-4-yloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 171.1° C.;

cis-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(2-chloro-4-methoxyphenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 172.9° C.;

A+b-1-[2-(2,4-dichlorophenyl)-4-(phenylmethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolediethanedioate; mp. 117.1° C.;

A+b-1-{2-(2,4-dichlorophenyl)-4-[(4-fluorophenyl)thiomethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolediethanedioate; mp. 129.8° C.;

A+b-1-[4-(4-chlorophenylmethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolesesquiethanedioate; mp. 141.6° C.

A+b-1-[2-(2,4-dichlorophenyl-4-(4-methoxyphenylmethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolediethanedioate; mp. 94.2° C.;

cis-2-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]-benzonitrilenitrate; mp. 162.1° C.; and

cis-butyl4-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]benzoatenitrate; mp. 90.5° C.

EXAMPLE CXX

A mixture of 17 parts of 1H-imidazole, 27.4 parts ofA+B-4-([1,1'-bisphenyl]-4-yloxymethyl)-2-(bromomethyl)-2-(3,4,5-trichlorophenyl)-1,3-dioxolaneand 135 parts of N,N-dimethylacetamide is stirred and refluxed for 5days. The reaction mixture is cooled and poured onto water. The productis extracted twice with 1,1'-oxybisethane. The combined extracts arewashed with water, dried, filtered and evaporated. The residue ispurified by column-chromatography over silica gel using trichloromethaneas eluent. The first fraction is collected and the eluent is evaporated.The residue is converted into the nitrate salt in 4-methyl-2-pentanoneand 2,2'-oxybispropane. The salt is filtered off and crystallized from amixture of acetonitrile and 2,2'-oxybispropane, yielding 3 parts ofcis-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(3,4,5-trichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 212.2° C. The second fraction is collected and the eluentis evaporated. The residue is converted into the nitrate salt in4-methyl- 2-pentanone and 2,2'-oxybispropane. The salt is filtered offand crystallized from a mixture of acetonitrile and 2,2'-oxybispropane,yielding 1.9 parts oftrans-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(3,4,5-trichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 158° C.

EXAMPLE CXXI

Following the procedure of Example CXX and using equivalent amounts ofthe appropriate starting materials, the following imidazoles andimidazole acid addition salts are prepared:

cis-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(4-bromo-2-chlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp. 161.8° C.;

trans-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(4-bromo-2-chlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp. 164.6° C.;

cis-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(2-naphthalenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp. 152.6° C.;

trans-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(2-naphthalenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 230.6° C.;

cis-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(2,4,5-trichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 199.2° C.; and

trans-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(2,4,5-trichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp. 139.2° C.

EXAMPLE CXXII

A mixture of 6.4 parts of 1H-imidazole, 10 parts ofA+B-2-(bromomethyl)-4-(3-chloro-[1,1'-biphenyl]-4-yloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolaneand 135 parts of N,N-dimethylacetamide is stirred and refluxed for 5days. The reaction mixture is allowed to cool to room temperature andpoured onto water. The product is extracted twice with1,1'-oxybisethane. The combined extracts are washed with water, dried,filtered and evaporated. The residue is crystallized from4-methyl-2-pentanone, yielding 2.2 parts (22%) oftrans-1-[4-(3-chloro-[1,1'-biphenyl]-4-yloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp. 140.8° C.

EXAMPLE CXXIII

A mixture of 10.2 parts of 1H-imidazole and 26.8 parts of sodiummethoxide solution 30% is stirred and refluxed for 15 minutes. Thenthere are added 90 parts of N,N-dimethylformamide. The methanol isdistilled off till internal temperature of about 130° C. After theaddition of another 90 parts of N,N-dimethylformamide, 50 parts ofA+B-4-([1,1'-biphenyl]-4-yloxymethyl)-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolaneare added portionwise at about 100° C. Upon completion, stirring iscontinued for 5 hours at reflux temperature. The reaction mixture ispoured onto a mixture of water and methylbenzene. The organic phase isseparated and stirred with activated charcoal. The latter is filteredoff and the filtrate is evaporated. The residue is purified twice bycolumn-chromatography over silica gel using a mixture oftrichloromethane and 1% of methanol as eluent. The pure fractions arecollected and the eluent is evaporated. The residue is crystallized from2-propanol, yielding 9.3 parts of cis-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp. 150.7° C.

EXAMPLE CXXIV

To a stirred sodium methoxide solution, prepared starting from 3.8 partsof sodium in 40 parts of methanol, are added 11 parts of 1H-imidazoleand 225 parts of N,N-dimethylformamide. The methanol is distilled offtill internal temperature of 150° C. Then there are added 19 parts ofA+B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-ethyl-1,3-dioxolane and thewhole is stirred and refluxed for 1 hour. The reaction mixture isallowed to cool to room temperature and poured onto water. The productis extracted three times with 1,1'-oxybisethane. The combined extractsare washed with water, dried, filtered and evaporated. The residue ispurified by column-chromatography over silica gel using a mixture oftrichloromethane and 1% of methanol as eluent. The first fraction iscollected and the eluent is evaporated. The residue is is converted intothe nitrate salt in 2,2'-oxybispropane. The salt is filtered off andcrystallized from a mixture of 2-propanol and 2,2'-oxybispropane,yielding 12 parts (56%) ofA+B-1-[2-(2,4-dichlorophenyl)-4-ethyl-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 149.1° C.

EXAMPLE CXXV

To a stirred sodium methoxide solution, prepared starting from 2.8 partsof sodium in 40 parts of methanol, are added 8 parts of 1H-imidazole and225 parts of N,N-dimethylformamide. The methanol is distilled off tillinternal temperature of 150° C. Then there are added 30 parts ofA+B-2-(4-bromo-2-chlorophenyl)-2-(bromomethyl)-4-ethyl-1,3-dioxolane andstirring is continued for 1 hour at reflux temperature. The reactionmixture is cooled and poured onto water. The product is extracted twicewith 2,2'-oxybispropane. The combined extracts are washed with water,dried, filtered and evaporated. The residue is purified bycolumn-chromatography over silica gel using a mixture oftrichloromethane and 2% of methanol as eluent. The pure fractions arecollected and the eluent is evaporated. The residue is converted intothe nitrate salt in 2,2'-oxybispropane. The salt is filtered off andcrystallized from a mixture of 4-methyl-2-pentanone and2,2'-oxybispropane, yielding 8.5 parts (26%) of A+B-1-[2-(4-bromo-2-chlorophenyl)-4-ethyl-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 162.2° C.

EXAMPLE CXXVI

Following the procedure of Example CXXV and using equivalent amounts ofthe appropriate starting materials, the following imidazole acidaddition salts are prepared:

    ______________________________________                                         ##STR46##                                                                    Ar            R        Acid Salt  Melting Point                               ______________________________________                                        2-ClC.sub.6 H.sub.4                                                                         C.sub.2 H.sub.5                                                                        HNO.sub.3  147.6° C.                            2-CH.sub.3C.sub.6 H.sub.4                                                                   C.sub.2 H.sub.5                                                                        HNO.sub.3  117.5° C.                            4-CH.sub.3C.sub.6 H.sub.4                                                                   C.sub.2 H.sub.5                                                                        HNO.sub.3  172.7° C.                            2,3,4-(Cl).sub.3C.sub.6 H.sub.2                                                             C.sub.2 H.sub.5                                                                        HNO.sub.3  176.4° C.                            2-BrC.sub.6 H.sub.4                                                                         C.sub.2 H.sub.5                                                                        HNO.sub.3  135.3° C.                            2,3-(Cl).sub.2C.sub.6 H.sub.3                                                               C.sub.2 H.sub.5                                                                        HNO.sub.3  140.3° C.                            3-ClC.sub.6 H.sub.4                                                                         C.sub.2 H.sub.5                                                                        HNO.sub.3  151.6° C.                            4-OCH.sub.3C.sub.6 H.sub.4                                                                  C.sub.2 H.sub.5                                                                        HNO.sub.3  157.1° C.                            2-CH.sub.3 -4-ClC.sub.6 H.sub.3                                                             C.sub.2 H.sub.5                                                                        HNO.sub.3  126.8° C.                            2-Cl-4-OCH.sub.3C.sub.6 H.sub.3                                                             C.sub.2 H.sub. 5                                                                       HNO.sub.3  117.7° C.                            3,4,5-(Cl).sub.3C.sub.6 H.sub.2                                                             C.sub.2 H.sub.5                                                                        HNO.sub.3  195.8° C.                            2-naphthyl    C.sub.2 H.sub.5                                                                        HNO.sub.3  195.1° C.                            2-OCH.sub.3 -4-ClC.sub.6 H.sub.3                                                            C.sub.2 H.sub.5                                                                        HNO.sub.3  131.8° C.                            2,4,5-(Cl).sub.3C.sub.6 H.sub.2                                                             C.sub.2 H.sub.5                                                                        HNO.sub.3  180.1° C.                            2,4-(Cl).sub.2C.sub.6 H.sub.3                                                               nC.sub.3 H.sub.7                                                                       HNO.sub.3  119.2° C.                            2,4-(Cl).sub.2C.sub.6 H.sub.3                                                               nC.sub.4 H.sub.9                                                                       HNO.sub.3  113.1° C.                            2,4-(Cl).sub.2C.sub.6 H.sub.3                                                               nC.sub.5 H.sub.11                                                                      HNO.sub.3  128.3° C.                            2,4-(Cl).sub.2C.sub.6 H.sub.3                                                               nC.sub.6 H.sub.14                                                                      HNO.sub.3   99.4° C.                            2,4-(Cl).sub.2C.sub.6 H.sub.3                                                               nC.sub.7 H.sub.15                                                                      2(COOH).sub.2                                                                            131° C.                              2,4-(Cl).sub.2C.sub.6 H.sub.3                                                               nC.sub.8 H.sub.17                                                                      2(COOH).sub.2                                                                            132.8° C.                            ______________________________________                                    

example cxxvii

a mixture of 32 parts of1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanone, 55 parts of1,2,3-propanetriol, 35 parts of 4-methylbenzenesulfonic acid, 96 partsof butanol and 360 parts of dimethylbenzene is stirred and refluxed for5 days with water-separator. The reaction mixture is cooled, washed witha potassium carbonate solution and with water, dried, filtered andevaporated. The residue is dissolved in a diluted ethanedioic acidsolution. The resulting solution is washed twice with 1,1'-oxybisethane.The aqueous phase is separated and neutralized with potassium carbonate.The product is extracted with trichloromethane. The extract is dried,filtered and evaporated. The residue is purified bycolumn-chromatography over silica gel using a mixture oftrichloromethane and 2% of methanol as eluent. The first fraction iscollected and the eluent is evaporated. The residue is converted intothe nitrate salt in 2,2'-oxybispropane. The salt is filtered off andcrystallized from a mixture of 4-methyl-2-pentanone and2,2'-oxybispropane, yielding 5.5 parts (9.8%) of A+B-1-[4-(butoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 101.8° C. The second fraction is collected and the eluentis evaporated. The residue is triturated in 1,1'-oxybisethane. Theproduct is filtered off and crystallized from a mixture of4-methyl-2-pentanone and petroleumether, yielding 9.75 parts ofA+B-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanol;mp. 128.1° C.

EXAMPLE CXXVIII

A mixture of 7.7 parts of 1H-imidazole, 8 parts ofcis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-methanol, 1part of potassium iodide and 180 parts of N,N-dimethylacetamide isstirred and reflux for 3 days. The reaction mixture is cooled andevaporated. Then there are added 50 parts of water and 300 parts oftrichloromethane to the residue. The whole is washed three times withwater, dried, filtered and evaporated. The residue is purified bycolumn-chromatography over silica gel using a mixture oftrichloromethane and 2% of methanol as eluent. The pure fractions arecollected and the eluent is evaporated, yielding 9.2 parts ofcis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanol;mp. 140° C.

EXAMPLE CXXIX

Following the procedure of Example CXXVIII and using an equivalentamount oftrans-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane-4-methanol asa starting material, there is obtained:

trans-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanol;mp. 129° C.

EXAMPLE CXXX

To a stirred mixture of 4 parts ofcis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanol,2.2 parts of iodomethane and 90 parts of N,N-dimethylformamide are added0.5 parts of sodium hydride dispersion 78%. Stirring is continued for 2hours at room temperature. The reaction mixture is poured onto water andthe product is extracted three times with 1,1'-oxybisethane. Thecombined extracts are washed with water and acidified with a nitric acidsolution in 1,1'-oxybisethane. The formed nitrate salt is filtered offand crystallized from 4-methyl-2-pentanone, yielding 2.2 parts (45%) ofcis-1-[2-(2,4-dichlorophenyl)-4-(methoxymethyl)-1,3-dioxolane-2-ylmethyl]-1H-imidazolenitrate; mp. 140° C.

EXAMPLE CXXXI

To a stirred mixture of 4 parts ofcis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanol,1.7 parts of bromoethane and 90 parts of N,N-dimethylformamide are added0.5 parts of sodium hydride dispersion 78%. The whole is stirred for 1hour at room temperature. The reaction mixture is poured onto water andthe product is extracted three times with 2,2'-oxybispropane. Thecombined extracts are washed with water and acidified with a nitric acidsolution in 2,2'-oxybispropane. The formed nitrate salt is filtered offand crystallized from a mixture of 4-methyl-2-pentanone and2,2'-oxybispropane, yielding 4.7 parts (93%) ofcis-1-[2-(2,4-dichlorophenyl)-4-(ethoxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 134.7° C.

EXAMPLE CXXXII

Following the procedure of Example CXXXI and using an equivalent amountof appropriate bromoalkane or bromoalkene in place of the bromoethaneused therein, the following imidazole acid addition salts are prepared:

cis-1-[2-(2,4-dichlorophenyl)-4-(propoxymethyl)-1,3-dioxolan-2-ylmethyl)-1H-imidazolenitrate; mp. 131.7° C.;

cis-1-[2-(2,4-dichlorophenyl)-4-(pentyloxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 78.6° C.;

cis-1-[2-(2,4-dichlorophenyl)-4-(hexyloxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 87.1° C.;

cis-1-[2-(2,4-dichlorophenyl)-4-(heptyloxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 80.7° C.;

cis-1-[2-(2,4-dichlorophenyl)-4-(octyloxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 73.4° C.; and

cis-1-[2-(2,4-dichlorophenyl)-4-(2-propenyloxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 116.3° C.

EXAMPLE CXXXIII

To a mixture of 4 parts oftrans-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanol,1.7 parts of bromoethane and 90 parts of N,N-dimethylformamide are added0.5 parts of sodium hydride dispersion 78% and the whole is stirred for2 hours at room temperature. The reaction mixture is poured onto waterand the product is extracted twice with 2,2'-oxybispropane. The combinedextracts are washed with water and taken up in 2,2'-oxybispropane. Thesolution is acidified with nitric acid. The formed nitrate salt isfiltered off and crystallized from 4-methyl-2-pentanone, yielding 3.5parts (69%) oftrans-1-[2-(2,4-dichlorophenyl)-4-(ethoxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 151.4° C.

EXAMPLE CXXXIV

To a stirred mixture of 2.5 parts of 1-chloro-4-(chloromethyl)-benzene,4 parts ofcis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanoland 90 parts of N,N-dimethylformamide are added 0.5 parts of sodiumhydride dispersion 78%. Stirring is continued for 5 hours at roomtemperature. The reaction mixture is poured onto water and the productis extracted twice with 2,2'-oxybispropane. The combined extracts arewashed with water, dried, filtered and acidified with nitric acid. Theformed nitrate salt is filtered off and crystallized from a mixture of4-methyl-2-pentanone and 2,2'-oxybispropane. The product is filtered offand recrystallized from a mixture of 4-methyl-2-pentanone and2,2'-oxybispropane, yielding 3.5 parts (56%) ofcis-1-[4-(4-chlorophenylmethoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 131.7° C.

EXAMPLE CXXXV

By repeating the procedure of Example CXXXIV and using an equivalentamount of an appropriate (chloromethyl)benzene in place of the1-chloro-4-(chloromethyl)benzene used therein, there are obtained:

cis-1-{4-[(4-bromophenyl)methoxymethyl]-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl}-1H-imidazolenitrate; mp. 101.4° C.; and

cis-1-{2-(2,4-dichlorophenyl)-4-[(4-fluorophenyl)methoxymethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolenitrate; mp. 107° C.

EXAMPLE CXXXVI

To a stirred mixture of 3.3 parts of2,4-dichloro-1-(chloromethyl)benzene, 5 parts ofA+B-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanoland 90 parts of N,N-dimethylformamide are added 0.5 parts of sodiumhydride dispersion 78% and stirring is continued for 3 hours at roomtemperature. The reaction mixture is poured onto water and the productis extracted three times with 2,2'-oxybispropane. The combined extractsare washed with water, dried, filtered and evaporated. The residue ispurified by column-chromatography over silica gel using trichloromethaneas eluent. The first fraction (A-isomer) is collected and the eluent isevaporated. The residue is converted into the nitrate salt in4-methyl-2-pentanone and 2,2'-oxybispropane. The salt is filtered offand recrystallized from a mixture of 4-methyl-2-pentanone and2,2'-oxybispropane at 0° C., yielding 2.9 parts (35%) ofcis-1-{2-(2,4-dichlorophenyl)-4-[(2,4-dichlorophenyl)methoxymethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolenitrate; mp. 96.9° C. The second fraction (B-isomer) is collected andthe eluent is evaporated. The residue is converted into the nitrate saltin 4-methyl-2-pentanone and 1,1'-oxybisethane. The salt is filtered offand recrystallized from a mixture of 4-methyl-2-pentanone and2,2'-oxybispropane, yielding 1.6 parts (19%) oftrans-1-{2-(2,4-dichlorophenyl)-4-](2,4-dichlorophenyl)methoxymethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolenitrate; mp. 131.9° C.

EXAMPLE CXXXVII

By repeating the procedure of Example CXXXVI and using an equivalentamount of 4-(chloromethyl)-1,1'-bisphenyl in place of the2,4-dichloro-1-chloromethylbenzene used therin, there are obtained:

cis-1-[4-([1,1'-biphenyl]-4-ylmethoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolediethanedioate; mp. 107.6° C.; and

trans-1-[4-([1,1'-biphenyl]-4-ylmethoxymethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 168° C.

EXAMPLE CXXXVIII

A mixture of 2.2 parts of (4-hydroxyphenyl) phenyl methanone, 4.2 partsofcis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethylmethanesulfonate, 2 parts of potassium carbonate and 68 parts ofN,N-dimethylformamide is stirred overnight at 100° C. The reactionmixture is cooled and poured onto water. The product is extracted twicewith 1,1'-oxybisethane. The combined extracts are washed with water,dried, filtered and evaporated. The residue is converted into thenitrate salt in 4-methyl-2-pentanone and 2,2'-oxybispropane, yielding4.5 parts (78%) ofcis-{4-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]phenyl}phenyl methanone nitrate; mp. 179° C.

EXAMPLE CXXXIX

Following the procedure of Example CXXXVIII and using an equivalentamount of an appropriate phenol in place of the (4-hydroxymethyl) phenylmethanone used therein, the following imidazoles and imidazole acidaddition salts are prepared:

cis-5-chloro-2-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]-4-methylphenylphenyl methanone ethanedioate; mp. 170.8° C.;

cis-methyl4-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]benzoatenitrate; mp. 167.8° C.;

cis-{2-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]-5-methylphenyl}phenylmethanone nitrate; mp. 145.4° C.;

cis-(4-chlorophenyl){2-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]-4-methoxyphenyl}methanone;mp. 168.3° C.;

cis-{2-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4ylmethoxy]-4-methoxyphenyl}phenylmethanone; mp. 149.2° C.;

cis-1-{2-(2,4-dichlorophenyl)-4-[3-(trifluoromethyl)phenoxymethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolenitrate; mp. 152.6° C.;

cis-1-{4-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]phenyl}ethanonenitrate; mp. 182.6° C.;

cis-methyl2-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]benzoatenitrate; mp. 140.5° C.; and

cis-1-{4-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethoxy]phenyl}-1-propanonenitrate; mp. 176.2° C.

EXAMPLE CXL

A mixture of 12.5 parts of 1,2-butanediol, 19 parts of1-(2-chloro-4-fluorophenyl)-2-(1H-imidazol-1yl)ethanone hydrochloride,16 parts of 4-methylbenzenesulfonic acid, 40 parts of 1-butanol and 225parts of dimethylbenzene is stirred and refluxed for 6 days withwater-separator. After cooling, the reaction mixture is filtered and thefiltrate is washed with a diluted sodium hydroxide solution and withwater. After the addition of 2,2'-oxybispropane, the whole is acidifiedwith a nitric acid solution. The formed nitrate salt is filtered off andcrystallized from a mixture of 4-methyl-2-pentanone and2,2'-oxybispropane, yielding 5.7 parts (22%) ofA+B-1-[2-(2-chloro-4-fluorophenyl)-4-ethyl-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 132.4° C.

EXAMPLE CXLI

Following the procedure of Example CXL and using equivalent amounts ofthe appropriate starting materials, the following imidazoles andimidazole acid addition salts are prepared:

A+b-1-[2-(4-bromophenyl)-4-ethyl-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 194.7° C.;

A+b-1-[2-(2,4-dibromophenyl)-4-ethyl-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 149.7° C.;

A+b-1-[4-ethyl-2-(2-thienyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 135.4° C.;

A+b-1-[2-(5-chloro-2-thienyl)-4-ethyl-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 164.3° C.;

A+b-1-[4-(chloromethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 166.1° C.;

A+b-1-[4-([1,1'-biphenyl]-4-ylmethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1Himidazolediethanedioate; mp. 116.8° C.;

A+b-1-[2-(2-(2,4-dichlorophenyl)-4-(4-fluorophenylmethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolesesquiethanedioate; mp. 153.1° C.;

A+b-1-{2-(2,4-dichlorophenyl)-4-[(4-methylphenyl)methyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolesesquiethanedioate; mp. 123.1° C.

A+b-1-[4-(4-bromophenylmethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolediethanedioate; mp. 128.8° C.;

A+b-1-{4-[2-([1,1'-biphenyl]-4-yl)ethyl]-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl}-1H-imidazolesequiethanedioate hemihydrate; mp. 143.9° C.; and

A+b-1-{2-(2,4-dichlorophenyl)-4-[2-(phenylmethyl)phenoxymethyl]-1,3-dioxolan-2-ylmethyl}-1H-imidazolesesquiethanedioate. hemihydrate; mp. 113° C.

EXAMPLE CXLII

A mixture of 13.8 parts of1-(2-chloro-4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanone hydrochloride,14.6 parts of 3-([1,1'-biphenyl]-4-yloxy)-1,2-propanediol, 16 parts of4-methylbenzenesulfonic acid, 40 parts of butanol and 225 parts ofdimethylbenzene is stirred and refluxed for one week withwater-separator. After cooling, 1,1'-oxybisethane is added and the wholeis washed successively with a diluted sodium hydroxide solution and withwater, dried, filtered and evaporated. The residue is purified bycolumn-chromatography over silica gel using trichloromethane as eluent.The first fraction (A-isomer) is collected and the eluent is evaporated.The residue is converted into the nitrate salt is 4-methyl-2-pentanoneand 2,2'-oxybispropane. The product is filtered off and crystallizedfrom a mixture of acetonitrile and 2,2'-oxybispropane, yielding 5 partsofcis-1-[4-([1,1'-bisphenyl]-4-yloxymethyl)-2-(2-chloro-4-fluorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 185.7° C. The second fraction (B-isomer) is collected andthe eluent is evaporated. The residue is converted into the nitrate saltin 4-methyl-2-pentanone and 2,2'-oxybispropane. The salt is filtered offand crystallized from a mixture of acetonitrile and 2,2'-oxybispropane,yielding 5.9 parts oftrans-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(2-chloro-4-fluorophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 156.9° C.

EXAMPLE CXLIII

Following the procedure of Example CXLII and using equivalent amounts ofthe appropriate starting materials, the following imidazoles andimidazole acid addition salts are prepared. When only one isomer islisted, no second fraction was obtained from chromatography.

cis-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(2-thienyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp. 149.5° C.;

trans-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(2-thienyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazole;mp.>300° C.;

cis-1-([1,1'-biphenyl]-4-yloxymethyl)-2-(2,4-dibromophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 174.4° C.;

trans-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(2,4-dibromophenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 141.8° C.; and

cis-1-[4-([1,1'-biphenyl]-4-yloxymethyl)-2-(5-chloro-2-thienyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 170° C.

EXAMPLE CXLIV

To a stirred mixture of 1.1 parts of 3-chloro-1-propyne, 4 parts ofcis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-methanoland 90 parts of N,N-dimethylformamide are added 0.5 parts of sodiumhydride dispersion 78%. Stirring is continued for 3 hours at roomtemperature. The reaction mixture is poured onto water and the productis extracted twice with 1,1'-oxybisethane. The combined extracts arewashed with water, dried, filtered and evaporated. The residue ispurified by column-chromatography over silica gel using a mixture oftrichloromethane and methanol (98:2) as eluent. The pure fractions arecollected and the eluent is evaporated. The residue is converted intothe ethanedioate salt in 4-methyl-2-pentanone and 2,2'-oxybispropane.The salt is filtered off and crystallized from 4-methyl-2-pentanone,yielding 3.6 parts (55%) ofcis-1-[2-(2,4-dichlorophenyl)-4-(2-propynyloxymethyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolediethanedioate; mp. 145.6° C.

EXAMPLE CXLV

A mixture of 17 parts of 1H-imidazole, 16 parts ofA+B-2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-ethenyl-1,3-dioxolane and225 parts of N,N-dimethylformamide is stirred and refluxed for 3 days.The reaction mixture is cooled, poured onto water and the product isextracted twice with 1,1'-oxybisethane. The combined extracts are washedwith water, dried, filtered and evaporated. The residue is purified bycolumn-chromatography over silica gel using trichloromethane as eluent.The pure fractions are collected and the eluent is evaporated. Theresidue is converted into the nitrate salt in 4-methyl-2-pentanone and2,2'-oxybispropane. The salt is filtered off and crystallized from4-methyl-2-pentanone, yielding 2.4 parts (13%) ofA+B-1-[2-(2,4-dichlorophenyl)-4-ethenyl)-1,3-dioxolan-2-ylmethyl]-1H-imidazolenitrate; mp. 150.9° C.

I claim:
 1. A chemical compound having the formula: ##STR47## wherein: Wis halo;Ar is a member selected from the group consisting of phenyl andsubstituted phenyl, wherein said substituted phenyl is phenyl havingfrom 1 to 3 substituents independently selected from the groupconsisting of halo, loweralkyl, loweralkyloxy, nitro and cyano; and R isalkenyl, wherein said alkenyl has from 2 to 10 carbon atoms.
 2. Thecompound of claim 1 wherein said W is bromo, said Ar is2,4-dichlorophenyl and said R is ethenyl.